Airway granulation response to lung-implantable medical devices:a concise overview

Increasing numbers of endoscopically implantable devices are implanted in the airways, such as airway stents, one-way valves and coils, to treat both malignant and benign diseases. They significantly improve patient outcomes, but their long-term effectiveness and sustainability is hampered by the reaction of the formation of granulation tissue. Factors including procedural-related tissue injury; micro-organism presence; device-related factors, such as the material, design and sizing in relation to the airway; and patient-related factors, including genetic susceptibility, comorbidities and medication use, might all effect the severity of the tissue response and the subsequent degree of granulation tissue formation. However, research into the underlying mechanism and risk factors is scarce and therefore our knowledge is limited. Joint efforts from the scientific community, both pre-clinical and clinical, are needed to gain a deeper understanding and eventually improve the long-term treatment effectiveness of lung-implantable devices

The cellular composition of the lung lining fluid gradually changes from bronchus to alveolus

Although large advances have recently been made mapping out the cellular composition of lung tissue using single cell sequencing, the composition and distribution of the cellular elements within the lining fluid of the lung has not been extensively studied. Here, we assessed the cellular composition of the lung lining fluid by performing a differential cell analysis on bronchoalveolar lavage fluid (BALF) and epithelial lining fluid (ELF) at four different locations within the lung in post-lung transplantation patients. The percentage of neutrophils and lymphocytes is reduced in more distal regions of the lungs, while the percentage of macrophages increases in these more distal regions. These data provide valuable information to determine which lung lining fluid sampling technique and location is best to use for measuring specific factors and biomarkers, and to increase the understanding of different cell populations in specific lung regions

The development, validation, and in vivo testing of a high-precision bronchial epithelial lining fluid sampling device.

INTRODUCTION: Analysis of respiratory biomarkers or pharmaceutical drug concentrations in bronchial epithelial lining fluid (bELF) using a high-precision sampling method is crucial for effective clinical respiratory diagnostics and research. Here, we utilized a cellulose matrix as an absorptive probe for bELF sampling, subsequently testing the design of a device and sampling technique in vivo. METHODS: The absorptive matrix [Whatman® qualitative filter paper (Grade CF-12)] was first tested through tissue-contact experiments on porcine airway tissue. The absorption and elution capacity of the matrix, as well as the laboratory processing and analysis method, was validated with a range of Interleukin-8 (CXCL8) and C-Reactive protein (CRP) stock solutions. Subsequently, the device's design was optimized for universal in-house production and both, safe and efficient sampling. The airway sampling method was then tested in a group of 10 patients with Chronic Obstructive Pulmonary Disease (COPD). For each patient, a bELF sample was obtained using the newly developed bELF probe, as well as a reference 20 mL saline bronchial wash sample. Supernatants were assessed, using an immunoassay, for levels of the pro-inflammatory markers CXCL8, Myeloperoxidase (MPO), and CRP. The bELF samples were compared to bronchial wash. RESULTS: The Whatman® qualitative filter paper (Grade CF-12) bELF probes adhered to porcine airway tissue, softening slightly upon wetting. The material maintained architectural integrity following the removal of the probes, leaving no residual fibers on the porcine airway mucosa. The bELF probe design was optimized for bronchoscopic delivery and in-house production. On average, a fully saturated bELF probe carried 32 μL of protein-rich fluid. The mean return of CXCL8 and CRP from samples collected from a serial dilution series (1, 5, 10, 20 ng/mL) was 69% (range 48%-87%). The bELF probe detected, on average, 7 (MPO), 14 (CRP), and 59 (CXCL8) times higher equivalent inflammatory protein concentrations in the collected bELF probe samples compared to the bronchial wash. CONCLUSION: The bELF probe is an effective absorptive technology for high-precision bELF sampling without dilution. With a simple in-house production procedure and bronchoscopic sampling technique, this method can be introduced in any bronchoscopic center for a consistent sampling of bELF.</p

Crosslink bio-adhesives for bronchoscopic lung volume reduction:current status and future direction

Several bronchoscopic lung volume reduction (BLVR) treatments have been developed to reduce hyperinflation in emphysema patients. Lung bio-adhesives are among the most promising new BLVR treatment options, as they potentially provide a permanent solution for emphysematous patients after only a single application. To date, bio-adhesives have mainly been used as haemostats and tissue sealants, while their application in permanently contracting and sealing hyperinflated lung tissue has recently been identified as a novel and enticing opportunity. However, a major drawback of the current adhesive technology is the induction of severe inflammatory responses and adverse events upon administration. In our review, we distinguish between and discuss various natural, semi-synthetic and synthetic tissue haemostats and sealants that have been used for pulmonary applications such as sealing air/fluid leaks. Furthermore, we present an overview of the different materials including AeriSeal and autologous blood that have been used to achieve lung volume reduction and discuss their respective advantages and drawbacks. In conclusion, we describe the key biological (therapeutic benefit and biocompatibility) and biomechanical (degradability, adhesive strength, stiffness, viscoelasticity, tunability and self-healing capacity) characteristics that are essential for an ideal lung bio-adhesive material with the potential to overcome the concerns related to current adhesives

A man with hypoxaemia after a femoral fracture

A 25-year-old male presented with fever and dyspnoea after a femoral fracture, which was treated with intramedullary nail fixation. Based on clinical criteria and a CT scan, the diagnosis fat embolism was made. He was treated conservatively and made a full recovery.</p

Design of the exhale airway stents for emphysema (EASE) trial: an endoscopic procedure for reducing hyperinflation

<p>Abstract</p> <p>Background</p> <p>Airway Bypass is a catheter-based, bronchoscopic procedure in which new passageways are created that bypass the collapsed airways, enabling trapped air to exit the lungs. The Exhale Airway Stents for Emphysema (EASE) Trial was designed to investigate whether Exhale^®Drug-Eluting Stents, placed in new passageways in the lungs, can improve pulmonary function and reduce breathlessness in severely hyperinflated, homogeneous emphysema patients (NCT00391612).</p> <p>Methods/Design</p> <p>The multi-center, randomized, double-blind, sham-controlled trial design was posted on <url>http://www.clinicaltrials.gov</url> in October 2006. Because Bayesian statistics are used for the analysis, the proposed enrollment ranged from 225 up to 450 subjects at up to 45 institutions. Inclusion criteria are: high resolution CT scan with evidence of homogeneous emphysema, post-bronchodilator pulmonary function tests showing: a ratio of FEV₁/FVC < 70%, FEV₁≤50% of predicted or FEV₁< 1 liter, RV/TLC≥0.65 at screening, marked dyspnea score ≥2 on the modified Medical Research Council scale of 0-4, a smoking history of at least 20 pack years and stopped smoking for at least 8 weeks prior to enrollment. Following 16 to 20 supervised pulmonary rehabilitation sessions, subjects were randomized 2:1 to receive either a treatment (Exhale^®Drug-Eluting Stent) or a sham bronchoscopy. A responder analysis will evaluate the co-primary endpoints of an FVC improvement ≥12% of the patient baseline value and modified Medical Research Council dyspnea scale improvement (reduction) ≥1 point at the 6-month follow-up visit.</p> <p>Discussion</p> <p>If through the EASE Trial, Airway Bypass is shown to improve pulmonary function and reduce dyspnea while demonstrating an acceptable safety profile, then homogeneous patients will have a minimally invasive treatment option with meaningful clinical benefit.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: NCT00391612</p