Validated respiratory drug deposition predictions from 2D and 3D medical images with statistical shape models and convolutional neural networks.

For the one billion sufferers of respiratory disease, managing their disease with inhalers crucially influences their quality of life. Generic treatment plans could be improved with the aid of computational models that account for patient-specific features such as breathing pattern, lung pathology and morphology. Therefore, we aim to develop and validate an automated computational framework for patient-specific deposition modelling. To that end, an image processing approach is proposed that could produce 3D patient respiratory geometries from 2D chest X-rays and 3D CT images. We evaluated the airway and lung morphology produced by our image processing framework, and assessed deposition compared to in vivo data. The 2D-to-3D image processing reproduces airway diameter to 9% median error compared to ground truth segmentations, but is sensitive to outliers of up to 33% due to lung outline noise. Predicted regional deposition gave 5% median error compared to in vivo measurements. The proposed framework is capable of providing patient-specific deposition measurements for varying treatments, to determine which treatment would best satisfy the needs imposed by each patient (such as disease and lung/airway morphology). Integration of patient-specific modelling into clinical practice as an additional decision-making tool could optimise treatment plans and lower the burden of respiratory diseases.

Exploring the role of advanced clinical practitioners (ACPs) and their contribution to health services in England: A qualitative exploratory study.

BACKGROUND: An extended role being explored globally is the advanced clinical practitioner (ACP). In England this is an extended role for allied health professions, nurses and midwives in a range of settings. OBJECTIVES: This paper focuses on three research questions: 1) What is the role of ACPs in England? 2) What are the barriers and facilitators to implementing the role? and 3) What is the contribution of ACPs to health services in England? DESIGN/SETTING: A qualitative, exploratory study to explore perspectives on the ACP role in a range of clinical settings. PARTICIPANTS: We recruited 63 stakeholders, including 34 nurses, working in a ACP role or ACP education. A purposive snowball sampling technique identified participants meeting inclusion criteria. METHODS: One-to-one semi-structured interviews throughout 2020, recorded and transcribed verbatim, anonymised and thematically analysed. RESULTS: The ACP role in England was undertaken in a broad range of clinical contexts. In England 'advanced clinical practitioner' was not a protected title. There were high levels of variability and ambiguity of understanding and deployment of the ACP role in England. Facilitators to the implementation process included training and education, clinical supervision and organisational support. Lack of protection for the role and variances in experience were barriers. Employer support facilitated development of the ACP role, however where support was limited, at either an individual or organisation level, this was a barrier. Our study highlighted the wide range of ways the ACP role benefitted patient outcomes and workforce development. CONCLUSIONS: This study outlines the contribution that ACPs can make to health services, contributing factors and key barriers and facilitators to implementing this role. The work showed the positive contribution ACPs can make to service redesign, workforce development and patient outcomes, whilst accepting there is much work to do to ensure protected status and parity across all professions and clinical contexts.

Pilot study of physiotherapist-led versus music therapist-led breathing control exercises for young adults living with breathing pattern disorder: a randomised controlled trial protocol.

INTRODUCTION: Breathing pattern disorder (BPD) is an abnormal breathing pattern associated with biochemical, biomechanical and psychophysiological changes. While physiotherapy is often offered, limited evidence-based therapies for BPD are available. Music therapy-based singing exercises have been shown to improve quality of life for individuals with respiratory conditions and may also be beneficial for individuals living with BPD. No study has previously compared these participatory interventions in the treatment of people living with BPD. METHODS AND ANALYSIS: This is a study protocol for an assessor blinded 1:1 randomised controlled trial and qualitative interview study. Forty participants aged 18-40 years who score at least 19 on the Nijmegen Questionnaire (NQ) and do not have any underlying respiratory conditions will be recruited. Participants will be randomised to receive either physiotherapy-led or music therapy-led breathing exercises for 6 weeks. The primary outcome will be between-group difference in NQ post-intervention. Semistructured interviews with a purposive sample of participants will be performed. Qualitative data will be analysed using thematic analysis to better understand participants' intervention and trial experiences. ETHICS AND DISSEMINATION: This study has received ethical approval by Brunel University London College of Health, Medicine and Life Science's Research Ethics Committee (32483-MHR-Mar/2022-38624-3). The anonymised completed dataset will be made available as an open-access file via Brunel University London Figshare and the manuscript containing anonymised patient data will be published in an open-access journal. TRIAL REGISTRATION NUMBER: This trial is registered on the Open Science Framework Registry (https://osf.io/u3ncw).

Playing the harmonica with chronic obstructive pulmonary disease. A qualitative study.

Objectives: To investigate the experience of playing the harmonica for individuals with COPD.Methods: A qualitative, phenomenological study using semi-structured interviews and reflexive thematic analysis.Results: Eight people living with COPD (six females, two males) were recruited, who had attended at least six weeks of harmonica group sessions, either face-to-face prior to the COVID-19 pandemic or remotely. Five themes were generated. Themes included 'hard in the beginning', 'holding the condition', 'breathing control', 'gives you a high' and 'needing the Zoom class'.Discussion: Playing the harmonica with COPD is difficult at first, particularly drawing a breath through the harmonica. With practice, experience in a fun activity and quality teaching, individuals were able to become more attuned and embodied with their breathing, and playing the harmonica offered a breathing control strategy. Songs, rather than breathing, became the focus, and participants were able to escape living with respiratory disease when playing. Participants reported the harmonica helped mucous expectoration. The group was a priority in the weekly lives of participants, even though the 'buzz' of being part of a group was lost when participating online. Further mechanistic studies and randomised controlled trials are needed to investigate the biopsychosocial benefits of playing the harmonica with COPD.

Nationwide evaluation of the advanced clinical practitioner role in England: a cross-sectional survey.

BACKGROUND AND STUDY OBJECTIVE: In response to growing pressures on healthcare systems, the advanced clinical practice (ACP) role has been implemented widely in the UK and internationally. In England, ACP is a level of practice applicable across various healthcare professions, who exercise a level of autonomy across four domains, referred to as the four pillars of practice (education, leadership, research and clinical practice). A national framework for ACP was established in 2017 to ensure consistency across the ACP role, however current ACP governance, education and support is yet to be evaluated. This study aimed to analyse data from a national survey of the ACP role to inform the development and improvement of policies relating to ACP in the National Health Service (NHS) in England. DESIGN: A cross-sectional survey with free-text comments. SETTING: The survey was distributed across primary and secondary levels of care to three distinct groups in England, including individual ACPs, NHS provider organisations and Trusts and primary care settings. PARTICIPANTS: A total of 4365 surveys were returned, from ACP staff (n=4013), NHS provider organisations and Trusts (n=166) and primary care organisations (n=186). RESULTS: Considerable variation was found in role titles, scope of practice, job descriptions and educational backgrounds of ACPs. Differing approaches to governance were noted, which led to inconsistent ACP frameworks in some organisations. A further challenge highlighted included committing time to work across the four pillars of advanced practice, particularly the research pillar. ACPs called for improvements in supervision and continuing professional development alongside further support in navigating career pathways. CONCLUSIONS: A standardised approach may support ACP workforce development in England and enable ACPs to work across the four pillars of practice. Due to the wide uptake of ACP roles internationally, this study has relevance across professions for global healthcare workforce transformation.

Gender differences in non-cystic fibrosis bronchiectasis severity and bacterial load: the potential role of hormones.

Non cystic-fibrosis bronchiectasis (NCFB) is a complex chronic respiratory disease, characterised by excessive sputum production and abnormal permanent dilation of bronchi. Mucus accumulation leads to recurrent bacterial infections and increased bacterial load, causing vicious cycles of structural damage and decreased lung function. Respiratory physiotherapy management of NCFB includes airway clearance techniques and use of nebulised, hypertonic saline. Despite advances in treatment, a consistent relationship has been observed between gender and disease occurrence, with a higher prevalence amongst females. Furthermore, NCFB presents most aggressively amongst post-menopausal females, a group likely exposed to higher levels of progesterone (P4) over a longer period of time. The effects of gender-specific hormones on bacterial load and physiotherapy management of people living with NCFB remain unknown. The aim of this narrative review was to discuss the potential influence of gender specific hormones on NCFB disease progression and influence on physiotherapy, medical management and future research. SCOPUS and PUBMED electronic databases were used to conduct searches for relevant studies using specific inclusion and exclusion criteria. Secondary inclusion of relevant literature was obtained from primary paper references. Previous literature suggests that P4 may impair Cilia Beat Frequency (CBF) in airway epithelium. Reduction in CBF may further reduce ability to expectorate amongst individuals with NCFB, increasing bacterial load and likelihood of exacerbations, negatively impacting on disease progression. Furthermore, coadministration of Estrogen has been suggested to offer opposing effects to that of P4 only. These findings question whether hormonal levels may be monitored, controlled and optimised within management and treatment of females with NCFB to improve airway clearance, reduce exacerbations and improve quality of life. Larger scale, long-term trials are required to further explore the effects of gender specific hormones on NCFB and the viability of treatment with hormone replacement therapy.The reviews of this paper are available via the supplemental material section.

Characterising the outcomes, impacts and implementation challenges of advanced clinical practice roles in the UK: a scoping review.

OBJECTIVES: In response to demographic and health system pressures, the development of non-medical advanced clinical practice (ACP) roles is a key component of National Health Service workforce transformation policy in the UK. This review was undertaken to establish a baseline of evidence on ACP roles and their outcomes, impacts and implementation challenges across the UK. DESIGN: A scoping review was undertaken following JBI methodological guidance. METHODS: 13 online databases (Medline, CINAHL, ASSIA, Embase, HMIC, AMED, Amber, OT seeker, PsycINFO, PEDro, SportDiscus, Osteopathic Research and PenNutrition) and grey literature sources were searched from 2005 to 2020. Data extraction, charting and summary was guided by the PEPPA-Plus framework. The review was undertaken by a multi-professional team that included an expert lay representative. RESULTS: 191 papers met the inclusion criteria (any type of UK evidence, any sector/setting and any profession meeting the Health Education England definition of ACP). Most papers were small-scale descriptive studies, service evaluations or audits. The papers reported mainly on clinical aspects of the ACP role. Most papers related to nursing, pharmacy, physiotherapy and radiography roles and these were referred to by a plethora of different titles. ACP roles were reported to be achieving beneficial impacts across a range of clinical and health system outcomes. They were highly acceptable to patients and staff. No significant adverse events were reported. There was a lack of cost-effectiveness evidence. Implementation challenges included a lack of role clarity and an ambivalent role identity, lack of mentorship, lack of continuing professional development and an unclear career pathway. CONCLUSION: This review suggests a need for educational and role standardisation and a supported career pathway for advanced clinical practitioners (ACPs) in the UK. Future research should: (i) adopt more robust study designs, (ii) investigate the full scope of the ACP role and (iii) include a wider range of professions and sectors.

Feasibility of an online platform delivery of pulmonary rehabilitation for individuals with chronic respiratory disease.

INTRODUCTION: SARS-CoV-2 has restricted access to face-to-face delivery of pulmonary rehabilitation (PR). Evidence suggests that telehealth-PR is non-inferior to outpatient PR. However, it is unknown whether patients who have been referred to face-to-face programmes can feasibly complete an online-PR programme. METHODS: This service evaluation used a mixed-methods approach to investigate a rapid PR service remodelling using the University of Gloucestershire eLearn Moodle platform. Quantitative baseline demographic and PR outcome data were collected from online-PR participants, and semistructured interviews were completed with PR staff and participants. RESULTS: Twenty-five individuals were eligible from a PR waiting list. Thirteen declined participation and 14 completed PR. Significant pre-post online PR improvements were achieved in 1 min sit-to-stand (CI 2.1 to 9 (p=0.004)), Generalised Anxiety Disorder (CI -0.3 to -2.6 (p=0.023)), Primary Health Questionnaire-9 (CI -0.3 to -5.1 (p=0.029)), Chronic Respiratory Questionnaire dyspnoea (CI 0.5 to 1.3 (p=0.001)), fatigue (CI 0.7 to 2 (p=0.0004)), emotion (CI 0.7 to 1.7 (p=0.0002)), mastery (CI 0.4 to 1.3 (p=0.001)). Interviews indicated that patient PR inclusion was made possible with digital support and a PR introduction session improved participant engagement and safety. Incremental progression of exercise was perceived as more successful online compared with face-to-face PR. However, perceptions were that education sessions were less successful. Online-PR required significant staff time resource. DISCUSSION: Online-PR improves patient outcomes and is feasible and acceptable for individuals referred for face-to-face PR in the context of a requirement for social distancing. Face-to-face programmes can be adapted in a rapid fashion with both staff and participants perceiving benefit. Future pragmatic trials are now warranted comparing online-PR including remote assessments to centre-based PR with suitably matched outcomes, and patient and staff perceptions sought regarding barriers and facilitators of online delivery.

Interrelationships Among Small Airways Dysfunction, Neutrophilic Inflammation, and Exacerbation Frequency in COPD.

BACKGROUND: Small airways disease (SAD) is a key component of COPD and is a main contributing factor to lung function decline. RESEARCH QUESTION: Is SAD a key feature of frequent COPD exacerbators and is this related to airway inflammation? STUDY DESIGN AND METHODS: Thirty-nine COPD patients defined as either frequent exacerbator (FE) group (≥ 2 exacerbations/y; n = 17) and infrequent exacerbator (IFE) group (≤ 1 exacerbation/y; n = 22) underwent the forced oscillation technique (resistance at 5 Hz minus 19 Hz [R5-R19], area of reactance [AX]), multiple breath nitrogen washout (conducting airways ventilation heterogeneity, acinar ventilation heterogeneity [Sacin]), plethysmography (ratio of residual volume to total lung capacity), single-breath transfer factor of the lung for carbon monoxide, spirometry (FEV1, FEV1/FVC), and paired inspiratory-expiratory CT scans to ascertain SAD. A subpopulation underwent bronchoscopy to enable enumeration of BAL cell proportions. RESULTS: Sacin was significantly higher in the COPD FE group compared with the IFE group (P = .027). In the FE group, markers of SAD were associated strongly with BAL neutrophil proportions, R5-R19 (P = .001, r = 0.795), AX (P = .049, ρ = 0.560), residual volume to total lung capacity ratio (P = .004, r = 0.730), and the mean lung density of the paired CT scans (P = .018, r = 0.639). INTERPRETATION: Increased Sacin may be a consequence of previous exacerbations or may highlight a group of patients prone to exacerbations. Measures of SAD were associated strongly with neutrophilic inflammation in the small airways of FE patients, supporting the hypothesis that frequent exacerbations are associated with SAD related to increased cellular inflammation.

Quantitative Assessment of Regional Mucociliary Clearance in Smokers with Mild-to-Moderate Chronic Obstructive Pulmonary Disease and Chronic Bronchitis from Planar Radionuclide Imaging.

Background: Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study investigates the value of regional clearance measurements in assessing MCC in mild-to-moderate disease. Methods: Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (i) healthy nonsmoking controls (NSCs) (n = 9), (ii) smoking controls (SCs) who were current smokers with normal lung function (n = 10), and (iii) current smokers with mild-to-moderate COPD and bronchitis (n = 15). The mean (±standard deviation) forced expiratory volumes at 1 second (FEV1) for the three groups were 109 (± 18), 94 (± 5), and 78 (± 12), respectively. After inhalation of a technetium-99m labeled aerosol, planar imaging was performed over 4 hours and then at 24 hours. Both lung clearance and tracheobronchial clearance (TBC) (normalized to 24 hours clearance) were calculated for inner and outer lung zones. Inner zone clearance was corrected for input from the outer zone. A novel parameter, the bronchial airways clearance index (BACI), which combined clearance data from both zones, was also evaluated. Regional results were compared with whole lung clearance in the same subjects. Results: Corrected inner zone clearance at 3 hours was not reduced compared with NSC in either SCs or COPD. Outer zone clearance was higher in COPD than in the other groups. Corrected inner zone TBC showed significant reductions in SC and COPD compared with NSC. BACI was significantly reduced in COPD compared with NSC and also correlated with FEV1. The mean BACI for SC was also reduced compared with NSC, but the distribution of results was bimodal, with a significant proportion of subjects having values in the NSC range. Conclusions: Regional MCC demonstrated differences between NSCs, SCs, and subjects with mild-to-moderate COPD, which were not apparent with whole lung measurements.

Characterising the evidence base for advanced clinical practice in the UK: a scoping review protocol.

INTRODUCTION: A global health workforce crisis, coupled with ageing populations, wars and the rise of non-communicable diseases is prompting all countries to consider the optimal skill mix within their health workforce. The development of advanced clinical practice (ACP) roles for existing non-medical cadres is one potential strategy that is being pursued. In the UK, National Health Service (NHS) workforce transformation programmes are actively promoting the development of ACP roles across a wide range of non-medical professions. These efforts are currently hampered by a high level of variation in ACP role development, deployment, nomenclature, definition, governance and educational preparation across the professions and across different settings. This scoping review aims to support a more consistent approach to workforce development in the UK, by identifying and mapping the current evidence base underpinning multiprofessional advanced level practice in the UK from a workforce, clinical, service and patient perspective. METHODS AND ANALYSIS: This scoping review is registered with the Open Science Framework (https://osf.io/tzpe5). The review will follow Joanna Briggs Institute guidance and involves a multidisciplinary and multiprofessional team, including a public representative. A wide range of electronic databases and grey literature sources will be searched from 2005 to the present. The review will include primary data from any relevant research, audit or evaluation studies. All review steps will involve two or more reviewers. Data extraction, charting and summary will be guided by a template derived from an established framework used internationally to evaluate ACP (the Participatory Evidence-Informed Patient-Centred Process-Plus framework). DISSEMINATION: The review will produce important new information on existing activity, outcomes, implementation challenges and key areas for future research around ACP in the UK, which, in the context of global workforce transformations, will be of international, as well as local, significance. The findings will be disseminated through professional and NHS bodies, employer organisations, conferences and research papers.

Spacers and Valved Holding Chambers-The Risk of Switching to Different Chambers.

Spacers are pressurized metered-dose inhaler (pMDI) accessory devices developed to reduce problems of poor inhaler technique with pMDIs. Spacers that feature a 1-way inspiratory valve are termed valved holding chambers (VHCs); they act as aerosol reservoirs, allowing the user to actuate the pMDI device and then inhale the medication in a 2-step process that helps users overcome challenges in coordinating pMDI actuation with inhalation. Both spacers and VHCs have been shown to increase fine particle delivery to the lungs, decrease oropharyngeal deposition, and reduce corticosteroid-related side effects such as throat irritation, dysphonia, and oral candidiasis commonly seen with the use of pMDIs alone. Spacers and VHCs are not all the same, and also are not interchangeable: the performance may vary according to their size, shape, material of manufacture and propensity to become electrostatically charged, their mode of interface with the patient, and the presence or otherwise of valves and feedback devices. Thus, pairing of a pMDI plus a spacer or a VHC should be considered as a unique delivery system. In this Rostrum we discuss the risk potential for a patient getting switched to a spacer or VHC that delivers a reduced dose medication.

A general framework in single and multi-modality registration for lung imaging analysis using statistical prior shapes.

BACKGROUND AND OBJECTIVE: A fusion of multi-slice computed tomography (MSCT) and single photon emission computed tomography (SPECT) represents a powerful tool for chronic obstructive pulmonary disease (COPD) analysis. In this paper, a novel and high-performance MSCT/SPECT non-rigid registration algorithm is proposed to accurately map the lung lobe information onto the functional imaging. Such a fusion can then be used to guide lung volume reduction surgery. METHODS: The multi-modality fusion method proposed here is developed by a multi-channel technique which performs registration from MSCT scan to ventilation and perfusion SPECT scans simultaneously. Furthermore, a novel function with less parameters is also proposed to avoid the adjustment of the weighting parameter and to achieve a better performance in comparison with the exisitng methods in the literature. RESULTS: A lung imaging dataset from a hospital and a synthetic dataset created by software are employed to validate single- and multi-modality registration results. Our method is demonstrated to achieve the improvements in terms of registration accuracy and stability by up to 23% and 54% respectively. Our multi-channel technique proposed here is also proved to obtain improved registration accuracy in comparison with single-channel method. CONCLUSIONS: The fusion of lung lobes onto SPECT imaging is achievable by accurate MSCT/SPECT alignment. It can also be used to perform lobar lung activity analysis for COPD diagnosis and treatment.

Quantitative Assessment of Mucociliary Clearance in Smokers with Mild-to-Moderate Chronic Obstructive Pulmonary Disease and Chronic Bronchitis from Planar Radionuclide Imaging Using the Change in Penetration Index.

Background: Mucociliary clearance (MCC) rate from the lung has been shown to be reduced in chronic obstructive pulmonary disease (COPD). This study compared the use of change in penetration index (PI) with conventional whole lung clearance in assessing MCC in mild-to-moderate disease. Methods: Measurement of lung MCC using planar gamma camera imaging was performed in three groups: (1) healthy nonsmoking controls (n = 9), (2) smoking controls who were current smokers with normal lung function (n = 10), and (3) current smokers with mild-to-moderate COPD and bronchitis (n = 15). The mean (±standard deviation) forced expiratory volume at 1 second (FEV1) for the three groups was 109 (±18), 94 (±5), and 78 (±12), respectively. Following inhalation of a technetium-99m labeled aerosol, planar imaging was performed over 4 hours and then at 24 hours. Total lung clearance and tracheobronchial clearance (TBC; normalized to 24-hour clearance) were calculated. A novel parameter, the normalized change in PI (NOCHIP), was also evaluated. PI is the ratio of counts between outer and inner lung zones normalized to lung volume. Results: More aerosol was deposited in central airways in COPD compared to nonsmoking controls, using 24-hour clearance measurements (p < 0.001). Smoking controls had intermediate values. The optimal endpoint for MCC assessment was chosen to be 3 hours, when intersubject variability was minimal, while preserving a measure of early clearance. There was no statistical difference between the three groups in mean total lung clearance, or TBC, at 3 hours. NOCHIP at 3 hours was reduced significantly, compared to nonsmoking controls, in both smoking controls (p = 0.007) and COPD (p < 0.0001). It also correlated with FEV1 (p = 0.003). A higher proportion of smoking control subjects had NOCHIP values in the nonsmoking control range than in the COPD group. Conclusions: NOCHIP was a more sensitive measure of MCC than whole lung clearance and TBC in mild-to-moderate COPD.

Systematic review of evidence for relationships between physiological and CT indices of small airways and clinical outcomes in COPD.

BACKGROUND: Small airways disease (SAD) is considered pivotal in the pathology of COPD. There are numerous publications describing physiological and Computed Tomography (CT) imaging markers to detect SAD. However, there is no agreed gold standard and limited understanding of the clinical associations of these measures to disease outcomes. METHODS: We conducted a systematic review using Embase, Medline and Pubmed to explore the relationship between physiological and CT SAD measures in COPD (GOLD Stages 1-4). Furthermore, evidence linking these physiological measures with defined clinical outcomes such as health status, functional assessment and exacerbation frequency were summarised. RESULTS: The search yielded 1160 abstracts of which 19 met the search criteria. Six studies examined physiological and CT measures while 13 publications identified physiological measures and clinical outcomes. Strong correlations were seen between CT and physiological measures of SAD. Varying associations between physiological measures and defined clinical outcomes were noted. CONCLUSIONS: Physiological and CT measures of SAD correlate and infer similar information. Physiological measures of SAD may offer valuable insight into clinical expression of the disease. A consensus on the standardisation and recommendation of tests to measure SAD is needed in order to better understand any clinical benefits of targeted drug therapy to the small airways.

Lung Topology Characteristics in patients with Chronic Obstructive Pulmonary Disease.

Quantitative features that can currently be obtained from medical imaging do not provide a complete picture of Chronic Obstructive Pulmonary Disease (COPD). In this paper, we introduce a novel analytical tool based on persistent homology that extracts quantitative features from chest CT scans to describe the geometric structure of the airways inside the lungs. We show that these new radiomic features stratify COPD patients in agreement with the GOLD guidelines for COPD and can distinguish between inspiratory and expiratory scans. These CT measurements are very different to those currently in use and we demonstrate that they convey significant medical information. The results of this study are a proof of concept that topological methods can enhance the standard methodology to create a finer classification of COPD and increase the possibilities of more personalized treatment.

Primary Air-Liquid Interface Culture of Nasal Epithelium for Nasal Drug Delivery.

Nasal drug administration is a promising alternative to oral and parenteral administration for both local and systemic delivery of drugs. The benefits include its noninvasive nature, rapid absorption, and circumvention of first pass metabolism. Hence, the use of an in vitro model using human primary nasal epithelial cells could be key to understanding important functions and parameters of the respiratory epithelium. This model will enable investigators to address important and original research questions using a biologically relevant in vitro platform that mimics the in vivo nasal epithelial physiology. The purpose of this study was to establish, systematically characterize, and validate the use of a primary human nasal epithelium model cultured at the air-liquid interface for the study of inflammatory responses and drug transport and to simultaneously quantify drug effects on ciliary activity.

Controlled, Parametric, Individualized, 2-D and 3-D Imaging Measurements of Aerosol Deposition in the Respiratory Tract of Asthmatic Human Subjects for Model Validation.

BACKGROUND: Computer modeling is used to predict inhaled aerosol deposition in the lung based on definition of the aerosol characteristics and the breathing pattern and airway anatomy of the subject. Validation of the models is limited by the lack of detailed experimental data. Three-dimensional imaging provides an opportunity to address this unmet need. METHODS: Radioactive aerosol was administered to six male asthmatic subjects on two occasions under carefully monitored input conditions. Input parameters varied in particle size, depth of breathing, and carrier gas. The aerosol distribution was measured by combined single photon emission computed tomography and x-ray computer tomography (SPECT/CT) and airway anatomy by high resolution CT. The deposition distribution was measured by both a 2D and 3D analysis and described in terms of the percentage of inhaled aerosol deposited in sections of the respiratory tract and in both spatial and anatomical subdivisions within each lung. The percentage deposition in the conducting airways was also assessed by 24 h clearance. RESULTS: A set of imaging data of aerosol deposition has thus been produced in which the input parameters of inhalation are well described. The results in asthmatics were compared to previous measurements in healthy controls using an identical inhalation protocol. The percentages of deposition in extra-thoracic and thoracic compartments of the airways were not significantly affected by disease, but the regional pulmonary deposition pattern was, with asthma leading to increased deposition in the conducting airways. CONCLUSIONS: The dataset acquired in this study will be useful in validating computer models of aerosol deposition in asthmatic subjects. Asthma did not affect the fraction of inhaled aerosol depositing in the lungs, but gave rise to a more central deposition pattern. The use of 3D SPECT imaging in combination with 24 h clearance measurements enables differentiation of deposition between bronchial and bronchiolar airways.

Regional assessment of lung function using thin-plate splines to align structural and functional imaging.

Ventilation / perfusion (VQ) Single Photon Emission Computed Tomography (SPECT) imaging provides 3D data of the regional distribution of ventilation and perfusion throughout the lung, but interpretation of the results is difficult without reference to the underlying lung anatomy. Multi-Slice Computed Tomography (MSCT) imaging is able to provide significant anatomical detail in the lung, allowing delineation of regional features such as the lobes. The purpose of this work was to develop software tools to allow the alignment of regions delineated from the MSCT scans, with the corresponding SPECT data, to allow measurements of VQ to be made for anatomically meaningful regions. The technique developed was based on the use of thin-plate splines and the results showed that it was able to provide good alignment between the MSCT and SPECT data.