3D Position Tracking using On-chip Magnetic Sensing in Image-guided Navigation Bronchoscopy.

This paper presents a compact and low-cost on-chip sensor and readout circuit. The sensor achieves high-resolution 5-degrees-of-freedom (DoF) tracking (x, y, z, yaw, and pitch). With the help of an external wire wound sensor, it can also achieve high-resolution 6-degrees-of-freedom (DoF) tracking (x, y, z, yaw, pitch, and roll angles). The sensor uses low-frequency magnetic fields to detect the position and orientation of instruments, providing a viable alternative to using X-rays in image-guided surgery. To measure the local magnetic field, a highly miniaturised on-chip magnetic sensor capable of sensing the magnetic field has been developed incorporating an on-chip magnetic sensor coil, analog-front end, continuous-time ΔΣ analog-to-digital converter (ADC), LVDS transmitter, bandgap reference, and voltage regulator. The microchip is fabricated using 65 nm CMOS technology and occupies an area of 1.06 mm2, the smallest reported among similar designs to the best of our knowledge. The 5-DoF system accurately navigates with a precision of 1.1 mm within the volume-of-intrest (VOI) of 15×15×15 cm3. The 6-DoF system achieves a navigation accuracy of 0.8 mm and an angular error of 1.1 degrees in the same VOI. These results were obtained at a 20 Hz update rate in benchtop characterisation. The prototype sensor demonstrates accurate position tracking in real-life pre-clinical in-vivo settings within the porcine lung of a live swine, achieving a reported worst-case registration accuracy of 5.8 mm.

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF. However, the extent to which rare variants, genome-wide, may contribute to the risk of IPF remains unknown. Objectives: We used whole-genome sequencing to investigate the role of rare variants, genome-wide, on IPF risk. Methods: As part of the Trans-Omics for Precision Medicine Program, we sequenced 2,180 cases of IPF. Association testing focused on the aggregated effect of rare variants (minor allele frequency ⩽0.01) within genes or regions. We also identified individual rare variants that are influential within genes and estimated the heritability of IPF on the basis of rare and common variants. Measurements and Main Results: Rare variants in both TERT and RTEL1 were significantly associated with IPF. A single rare variant in each of the TERT and RTEL1 genes was found to consistently influence the aggregated test statistics. There was no significant evidence of association with other previously reported rare variants. The SNP heritability of IPF was estimated to be 32% (SE = 3%). Conclusions: Rare variants within the TERT and RTEL1 genes and well-established common variants have the largest contribution to IPF risk overall. Efforts in risk profiling or the development of therapies for IPF that focus on TERT, RTEL1, common variants, and environmental risk factors are likely to have the largest impact on this complex disease.

Single Use or Disposable Flexible Bronchoscopes: Bench Top and Preclinical Comparison of Currently Available Devices.

BACKGROUND: Data regarding the risk of infection related to reusable bronchoscopes, the global drive toward disposable technology and the COVID-19 pandemic have led to an increase in the use and production of single use or disposable bronchoscopes. An in-depth comparison of all available devices has not been published. METHODS: A benchtop comparison of the Ambu®aScopeTM, Boston Scientific® EXALTTM Model B, the Surgical Company Broncoflex© Vortex, Pentax® Medical ONE Pulmo™, and Vathin® H-SteriscopeTM (all 2.8 mm inner dimension other than the Pentax single-use flexible bronchoscope (3 mm)) was undertaken including measurement of maximal flexion and extension angles, thumb force required and suction with and without biopsy forceps. Thereafter, preclinical assessment was performed with data collected including experience, gender, hand size, and scope preference. RESULTS: The Vathin single-use flexible bronchoscope had the biggest range of tip movement from flexion to extension with and without forceps. The Boston single-use flexible bronchoscope required the maximal thumb force but had the least reduction of tip movement with forceps. The Boston single-use flexible bronchoscope significantly outperformed all other scopes including the standard Pentax scope and was the only scope capable of suctioning pseudo-mucus around the forceps. Although there was no significant difference in preference in the overall group, females and those with smaller hand size preferred the Pentax and males the Broncoflex single-use flexible bronchoscope. CONCLUSIONS: Currently available single-use flexible bronchoscopes differ in several factors other than scope sizes and monitor including suction, turning envelope, and handle size. Performance in the clinical setting will be key to their success.

Meta-Analysis on Utility of Bronchoscopy in Addition to Computed Tomography Thorax in the Investigation of Lung Cancer in Patients with Haemoptysis.

BACKGROUND: In patients with haemoptysis, many healthcare systems support bronchoscopy regardless of computed tomography (CT) findings. OBJECTIVE: This meta-analysis aimed to address whether a normal CT alone is sufficient to out-rule lung cancer in patients with haemoptysis. METHODS: A search was performed of the following databases: EBSCO (Medline), PubMed, Academic Search Complete, CINAHL, Cochrane Library, and Embase. Meta-Disc 1.4 and RevMan software were used to test for heterogeneity, risk of bias, and to summarize the test performance characteristics using forest plots and summary receiver operating characteristic (SROC) curves. SPSS was used to compare the diagnostic accuracy of CT and bronchoscopy. RESULTS: A total of 14 studies (2,960 patients) were included. The pooled sensitivities for detection of lung cancer using CT scan and bronchoscopy were 0.99 (95% CI: 0.97-1.00) and 0.84 (95% CI: 0.78-0.88), respectively. The sensitivity of CT was higher than that of bronchoscopy (p < 0.001). The pooled specificities for CT scan and bronchoscopy were 0.99 (95% CI: 0.99-1.00) and 1.00 (95% CI: 0.99-1.00), respectively. Of 2,960 patients, 257 had lung cancer (8.7%) at initial investigation. 254 of these had a CT thorax, and the CT scan was false negative in 4/255 (1.6%), with bronchoscopy only identifying one cancer with a normal CT (0.4%). CONCLUSION: CT scan showed a higher diagnostic accuracy than bronchoscopy. This study indicated that bronchoscopy offers an insignificant additional value in the investigation of lung cancer in patients with haemoptysis and a negative CT scan.

Single-Use or Disposable Flexible Bronchoscopy in Advanced Bronchoscopy Procedures: Experience in a Quaternary Referral Centre.

BACKGROUND: The development of single-use flexible or disposable bronchoscopes (SUFBs) has accelerated in recent years, with the reduced risk of infectious transmission and reduced need for endoscopy staffing particularly advantageous in the COVID-19 pandemic era. OBJECTIVE: The objective of this study was to assess the performance of a novel single-use bronchoscope in an academic quaternary referral centre with on-site interventional pulmonology programme. METHODS: With ethical approval in a quaternary referral centre, we prospectively collected data on sequential bronchoscopy procedures using The Surgical Company Broncoflex© range of SUFBs. Data collected included demographic, procedural, scope performance, user satisfaction, and complication parameters in a tertiary bronchoscopy service. RESULTS: 139 procedures were performed by five pulmonology faculty from January to July 2021. The majority were carried out for infection (45%) and malignancy (32%). Most were performed in the endoscopy suite and 8% were COVID positive or suspected. Most procedures reported the highest score in satisfaction (85%) with technical limitations reported in 15% (predominately related to scope suction or inadequate image quality) reverting to a reusable scope in 2.8 %. CONCLUSION: In our subset of patients in a bronchoscopy unit, SUFBs are safe, and both routine and advanced bronchoscopy procedures can be performed with high satisfaction reported.

Breathlessness and Respiratory Disability After Kidney Transplantation.

BACKGROUND: Dyspnea is a common symptom in patients with end-stage kidney disease being treated with dialysis. This study aimed to ascertain the level of respiratory disability in patients after kidney transplantation through assessing a cohort of kidney allograft recipients for respiratory compromise and thereby identifying a potential target for therapeutic intervention. METHODS: Kidney transplant recipients who were under active observation in a single tertiary referral center were invited to take part in this prevalence study at the time of clinic follow-up. All patients agreed to take part in the study, which involved completing a Medical Research Council (MRC) dyspnea scale, completing the St George's Respiratory Questionnaire, and performing basic spirometry. An MRC score of ≥2 and/or a forced expiratory volume in 1 second <90% predicted prompted formal clinical assessment by a respiratory physician. RESULTS: This study enrolled 103 patients; 35% of all patients reported breathlessness, and 56% of all patients warranted formal respiratory medicine review. After completion of their investigations, 33 patients were found to have an underlying condition accounting for their symptoms. CONCLUSION: Our study highlights the issues of respiratory disability and breathlessness in patients who have undergone kidney transplantation. Although extensive cardiologic evaluation is performed routinely and can rule out many causes of dyspnea, respiratory assessment is not a preoperative prerequisite. This study could suggest that a formal pulmonological evaluation and basic spirometry should be part of the pretransplant evaluation of the kidney transplant recipient.

Pulmonary Therapy Podcast-COVID-19: Research and Real-World Experiences from the Editorial Board.

The Editorial Board have prepared a podcast describing their experiences over the past year of the COVID-19 pandemic. The Editorial Board describe how COVID-19 impacted their research and how the initial clinical response changed over the course of the year in terms of treatment, personal protective equipment (PPE), and policy changes. The podcast and transcript can be viewed below the abstract of the online version of the manuscript. Alternatively, the podcast and transcript can be downloaded here: https://doi.org/10.6084/m9.figshare.14402291 Pulmonary Therapy Podcast-COVID-19: Research and Real-World Experiences from the Editorial Board (MP4 160260 KB).

Can single-use bronchoscopes help prevent nosocomial COVID-19 infections?

Introduction: The reduction of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission has been achieved through numerous public health initiatives worldwide. In the hospital environment, certain high-risk procedures have the potential to cause transmission of the virus to health-care workers and nosocomial transmission to patients through different mechanisms including the generation of aerosols and fomite formation via contamination of medical devices.Areas covered: Aerosol-generating procedures such as bronchoscopy are considered high risk for SARS-CoV-2 transmission. As a result, single-use devices should be used where possible and changing to single-use flexible bronchoscopes has been advised by respiratory societies internationally. In this paper, we outline the rationale for this advice and have analyzed the evidence relating to the reduction in SARS-CoV-2 transmission arising from a switch to these single-use devices and the potential impact that this switch may have on the quality of pulmonology services.Expert opinion: In this paper, we outline the rationale for this advice and have analyzed the evidence relating to the reduction in SARS-CoV-2 transmission arising from a switch to these single-use devices and the potential impact that this switch may have on the quality of pulmonology services.

Endobronchial Balloon Blockers: A Retrospective Analysis of Their Implementation for Use in Transbronchial Cryobiopsy Under Conscious Sedation.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is a promising technique that is evolving as a standard diagnostic procedure in the diagnosis of interstitial lung disease. However, there are a variety of non-standardised techniques adopted for this procedure. We aim to describe our approach to TBLC with balloon blockade under conscious sedation (CS). METHODS: We performed a retrospective analysis of patients undergoing TBLC using flexible bronchoscopy under CS in our institution over the calendar years 2017-2018; before and after a transition to the use of endobronchial balloon blockers (EBB) in 2017. RESULTS: 25 patients underwent transbronchial cryobiopsy during the study period. Of these; 12 procedures used EBB. EBB subjects had significantly less moderate or severe airway bleeding (8.3% vs 38.5%) despite higher biopsy rates in the EBB group, 2.9 (2-4) vs 2.4 (1-4) in the non-EBB group. No severe airway bleeding occurred in the EBB group. A multidisciplinary meeting (MDM) confirmed diagnosis was achieved in 88% of patients. 10/12 subjects (83%) in the EBB group and 12/13 subjects (92%) in the non-EBB group (p = 0.5). CONCLUSION: Our institution is novel in using EBB as standard during TBLC specifically under CS with flexible bronchoscopy in the bronchoscopy suite. This retrospective analysis demonstrates that EBB enhances the safety profile of performing TBLC under CS and did not appear to impact diagnostic yield or patient safety.

Transbronchial lung cryobiopsy (TBLC) in the diagnosis of interstitial lung disease: experience of first 100 cases performed under conscious sedation with flexible bronchoscope.

BACKGROUND: Diagnosing the aetiology of interstitial lung disease (ILD) may require histology via a surgical lung biopsy (SLB). SLB is associated with significant complications. Transbronchial lung cryobiopsy (TBLC) can provide large, adequate biopsies with fewer complications offering a potential alternative to SLB. AIMS: This study evaluated the safety, diagnostic yield and impact of TBLC on diagnostic certainty in the multidisciplinary diagnosis (MDD) of ILD within routine clinical practice. METHODS: A retrospective study of all TBLC performed in a tertiary institute from March 2014 to December 2016 was performed. Procedures were performed using a flexible bronchoscope and cryoprobe without fluoroscopic guidance. RESULTS: One hundred procedures were performed on 85 patients. A total of 272 cryobiopsies were obtained with a mean biopsy diameter of 5.9 ± 3.2 mm. Ninety-seven percent contained alveolated lung tissue. Diagnosis based against MDD gold standard was confirmed using TBLC in 67.1% of patients and in 72/100 procedures. Three patients proceeded to SLB. The addition of histological information changed the clinic-radiological diagnosis in twelve patients. The most common diagnosis based on clinical-radiologic-pathologic correlation at MDD was idiopathic pulmonary fibrosis (IPF) (51.2%) and hypersensitivity pneumonitis (15.9%). Moderate bleeding occurred in 18% of cases and five patients (5%) developed pneumothorax requiring intervention. Eleven patients required admission, with a mean length of stay of 1.3 ± 0.9 days. CONCLUSION: TBLC aids the diagnosis of ILD in the appropriate patient and may be an acceptable alternative to SLB with fewer complications. Further work on standardizing the procedure is required.

Single-Use (Disposable) Flexible Bronchoscopes: The Future of Bronchoscopy?

The coronavirus disease (COVID-19) pandemic has highlighted the importance of reducing occupational exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The reprocessing procedure for reusable flexible bronchoscopes (RFBs) involves multiple episodes of handling of equipment that has been used during an aerosol-generating procedure and thus is a potential source of transmission. Single-use flexible bronchoscopes (SUFBs) eliminate this source. Additionally, RFBs pose a risk of nosocomial infection transmission between patients with the identification of human proteins, deoxyribonucleic acid (DNA) and pathogenic organisms on fully reprocessed bronchoscopes despite full adherence to the guidelines. Bronchoscopy units have been hugely impacted by the pandemic with restructuring of pre- and post-operative areas, altered patient protocols and the reassessment of air exchange and cleaning procedures. SUFBs can be incorporated into these protocols as a means of improving occupational safety. Most studies on the efficacy of SUFBs have occurred in an anaesthetic setting so it remains to be seen whether they will perform to an acceptable standard in complex respiratory procedures such as transbronchial biopsies and cryotherapy. Here, we outline their potential uses in a respiratory setting, both during and after the current pandemic.

Hyponatremia and hypercalcemia: a study of a large cohort of patients with lung cancer.

BACKGROUND: Hyponatremia and hypercalcemia are reported to be associated with poorer prognosis in lung cancer. Our study assessed the incidence of hyponatremia and hypercalcemia in a recent large cohort of patients diagnosed with lung cancer in an academic institution and correlated incidence with patient and tumour parameters. METHODS: All patients presented at our regional lung cancer multidisciplinary team meeting between January 2011 and December 2016 were included. The incidence of hyponatremia (serum sodium ≤135 mEq/L) and hypercalcemia (serum calcium >2.62 mmol/L), including severity (mild, moderate or severe) was evaluated and stratified by tumour subtype and stage, and correlated with patient parameters. RESULTS: A total of 624 patients (mean age, 67.4 years; 59.3% male) diagnosed with tissue-proven lung cancer were included. Hyponatremia and hypercalcemia were present in 31.6% (n=197) and 7.1% (n=44) at time of diagnosis. Hyponatremia occurred most commonly in patients with small cell lung carcinoma (SCLC) (n=42; 41.2%; P=0.001). Hypercalcemia occurred most commonly in patients with non-small cell lung carcinoma (NSCLC) squamous subtype (n=27; 12.2%; P=0.003). The incidence of hyponatremia and hypercalcemia were significantly higher in the advanced stages (P<0.041), except in SCLC where no difference in hypercalcemia incidence across the stages was observed (P=0.573). The Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score was positively correlated with severity of hyponatremia at the early stage of NSCLC (Spearman correlation coefficient =0.325; P=0.003). CONCLUSIONS: Hyponatremia is a common association in lung cancer, especially in SCLC. Hypercalcemia is an uncommon but significant association in the NSCLC squamous subtype. Hyponatremia might contribute to poorer ECOG-PS scores at the early stage of NSCLC.