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New techniques in diagnosis and treatment of respiratory disease

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1J. H. Ward, 1A. Nair, 2B. J. Lipworth. 1Ninewells Hospital and Medical School, Dundee, UK, 2Asthma and Allergy Research Group, Ninewells Hospital and Medical School, Dundee, UK

Introduction Reversible airflow obstruction is often used as a criterion to support a clinical diagnosis of asthma. Bronchodilator reversibility is conventionally measured by forced expiratory spirometric manoeuvres, but is effort dependent and requires patient cooperation. Impulse oscillometry (IOS) is an effort-independent and patient-friendly lung function technique which appears to be an attractive alternative, but there are limited data correlating the bronchodilator response using the two techniques in adults with asthma and healthy volunteers.

Objectives To correlate clinical measurements performed by spirometry and IOS in response to administration of a bronchodilator in adults with asthma and healthy volunteers.

Methods The study was a prospective audit of ptients with asthma and healthy volunteers attending routine screening at a research unit in a university teaching hospital. Reversibility testing was carried out using standardised ATS/ERS criteria after administering 400 μg of sallbutamol via a valved spacer device. Spirometric (forced expiratory volume in 1 s (FEV1)) and IOS measurements (R5, R20, X5) were as per ERS/ATS guidelines.

Results Ninety-five patients with asthma and 61 healthy volunteers underwent screening. The mean percentage predicted (SEM) baseline prebronchodilator FEV1 was 83.99 (2.23) for those with asthma and 99.25 (1.72) for healthy volunteers. Baseline percentage predicted oscillometry indices in the group with asthma were 162.22 (7.5) for R5; 154.73 (4.71) for R20; and 441.72 (173.86) for X5. In the healthy volunteers this was 111.01 (3.96) for R5; 127.75 (4.12) for R20; and −229.80 (125.75) for X5.R5 was the only impulse oscillometry measure that showed correlation with spirometric indices (FEV1). The mean percentage predicted (SEM) postbronchodilator change in FEV1 and R5 in the group with asthma was 6.35 (0.65) and −33.78 (4.43), respectively; correspondingly in healthy volunteers it was 2.24 (0.32) and −14.91 (2.48). A negative correlation was demonstrated r = −0.40, p<0.001 between the two indices. Linear regression modelling demonstrated that a 1 unit change in %FEV1 corresponds to a 2.5% change in %R5.

Conclusions Low frequency IOS (R5) and spirometric measurements correlate. Linear regression allows prediction of this change. Further studies need to be carried out to ascertain the reproducibility of this measure prior to use in clinical practice.


1E. Lau, 1D. H. Brand, 1J. A. Usher-Smith, 2R. Wareham, 2J. Cameron, 1P. Bridge, 3W. Hills, 3G. Roberts, 1R. Iles, 2J. Lasenby. 1Addenbrooke’s Hospital NHS Trust, Cambridge, UK, 2Cambridge University Engineering Department, Cambridge, UK, 3PneumaCare Ltd, Cambridge, UK

Introduction This abstract presents a non-invasive monitoring method called structured light plethysmography1 (SLP) (PneumaScan) and compares its measurements of forced expiratory volumes with those from pneumatach spirometry (PNT).

Methods Simultaneous SLP and PNT measurements were made on 27 healthy subjects (20 males; age 9–61 years; body mass index 15.9–33.6) during a forced expiratory manoeuvre. A grid of black and white squares was projected onto the subjects’ chest and abdominal wall, ensuring coverage from the sternal notch superiorly to the anterior superior iliac crests inferiorly. Movements of the grid were captured by two digital cameras and recorded changes in volume. Algorithmic data reconstruction and analysis enabled forced expiratory volumes to be calculated. Subjects wore a plain, light coloured and tight-fitting T-shirt whilst standing against a black backdrop. The subjects’ backs were fixed to the wall at three different points (the occiput, the scapulae and the sacrum) to minimise movement. Concurrent measurements were made using a MasterScope spirometer and exported via the manufacturer’s J-scope software. Data were normalised to forced vital capacity (FVC), and drifts resulting from BTPS (body temperature and pressure and saturated with water vapour) corrections and integration errors were removed to allow direct comparison of SLP and PNT data.

Results Using paired Student t test, SLP data showed a high degree of agreement with PNT for forced expiratory volume in 1 s (FEV1) and FEV1/FVC (p = 0.085 and p = 0.1752, respectively). Pearson correlation coefficients for FEV1 and FEV1/FVC were both >0.85. In addition a Bland–Altman analysis showed no volume-related changes in trend differences.

Conclusion Forced expiratory volumes from SLP are comparable with those obtained by traditional pneumatach spirometry. SLP thus provides an alternative to pneumatach spirometry for measurement of forced expiration. Ongoing work is being undertaken to automate and refine the method.



1D. H. Brand, 1E. Lau, 1J. A. Usher-Smith, 2R. Wareham, 2J. Cameron, 1P. Bridge, 3W. Hills, 3G. Roberts, 2J. Lasenby, 1R. Iles. 1Addenbrooke’s Hospital NHS Trust, Cambridge, UK, 2Cambridge University Engineering Department, Cambridge, UK, 3PneumaCare Ltd, Cambridge, UK

Introduction Measurements of tidal breathing can be used in the diagnosis of respiratory disease. We present a novel, non-invasive lung function device, structured light plethysmography1 (SLP) (PneumaScan), and the results of a comparison of tidal breathing measured by SLP with those measured by traditional pneumatachography.

Method SLP utilises two digital cameras to track the 3D position of a checkerboard grid projected onto the subject’s anterior chest and abdominal wall. Data from 23 healthy adult subjects, aged 19–61, wearing relatively tight clothing, were collected in lying, sitting and standing positions (n = 69). Algorithmic data reconstruction and analysis enabled tidal breathing parameters to be calculated. Simultaneous pneumatach and SLP signals were collected for 1 min in each position. Parameters investigated were respiratory rate (RR), tidal volume (TV), inspiratory (IT) and expiratory (ET) times. As SLP currently produces relative volumes, data were scaled to the pneumatach data in order to obtain real number volumes for comparative purposes.

Results Pearson correlation r2 values were calculated for RR (r2 = 0.999, p<0.001), TV (r2 = 0.964, p<0.001), IT (r2 = 0.978, p<0.001) and ET (r2 = 0.988, p<0.001). Paired Student t test analysis showed no statistically significant difference between means in RR (p = 0.9071), TV (p = 0.6968), IT (p = 0.7328) or ET (p = 0.9134). Analysis of the differences in measurements between the SLP and pneumatach data is summarised in table 1. Different body positions made no statistically significant difference in correlation between SLP and pneumatach.

Conclusions Excellent correlation was seen between SLP and the pneumatach across all parameters. CIs for the means of differences were narrow. In this application SLP is a clinical device comparable with a pneumatach. Good agreement in the supine position may lead to application in continuous surveillance of tidal breathing. Ongoing work will enable independent automatic volume calibration of the SLP system.

Abstract S101 Table 1



1A. R. C. Patel, 2S. Jamal, 1K. Kumar, 2S. Lear, 2M. Lowdell, 2F. Tahami, 1M. Beckles, 2R. Chee, 1M. C. I. Lipman. 1Department of Respiratory Medicine, Royal Free Hospital, London, UK, 2Department of Immunology, Royal Free Hospital, London, UK

Background Bronchoalveolar lavage (BAL) cell fluid analysis can be helpful in the diagnosis and management of certain pulmonary diseases. This is generally performed using microscopy, with immunohistochemistry delineating specific cell subtypes. However, this is labour-intensive, time-consuming and potentially subject to operator bias. Flow cytometry allows rapid, automated and high-volume cell enumeration. Here we evaluate its use in assessing BAL differential cell counts in a hospital, respiratory population.

Methods A single-centre, retrospective review of adults with a clinical indication for BAL between October 2006 and June 2009. Using a four-colour flow cytometer, a filtered and concentrated portion of the sample was stained using combinations of monoclonal antibodies against CD45 (pan-leucocyte marker), CD3, CD4, CD8 (lymphocyte), CD15 (neutrophil) and CD23 (eosinophil marker). A minimum of 100 000 events were captured, yielding at least 5000 events within lymphocyte or granulocyte pools. Outcome measures were intra-assay variability (IAV) and the relationship between BAL cellular differential count and final clinical diagnosis.

Results Complete clinical and laboratory information was available on 118 of 124 patients. IAV was assessed using 10 randomly selected samples, with assays run in triplicate. The coefficient of variance was good, with a median value of <2% (range 0–9%). 31 patients had suspected pulmonary sarcoidosis prebronchoscopy. In the 20 (65%) who had the diagnosis confirmed, the median CD4:CD8 ratio was 4.4 (interquartile range (IQR) 2.7–8.3) compared with 0.7 (0.5–1.0) in the remainder who had an alternative diagnosis (p<0.001). Eight of 33 suspected tuberculosis cases were confirmed to have it. Their median lymphocyte percentage of total BAL cells was 59% (IQR 51–61%) vs 9% (4–24.5%) in the other 25 cases (p = 0.001). The percentage of neutrophils in the BAL cell population was significantly higher in bacterial infection (median 15%, IQR 8.8%–30%) compared with other non-bacterial infections (4%, 2–10%, p = 0.007). Table 1 gives median (IQR) cellular differentials for conditions with >2 cases (n = 104).

Conclusions BAL fluid can be analysed using flow cytometry in a routine laboratory setting. The technique is straightforward, precise and appears to discriminate specific clinical processes. Further work needs to determine whether this adds value to other current diagnostic investigations.

Abstract S102 Table 1


1N. Navani, 1H. L. Booth, 2B. Sheinman, 3N. Johnson, 1S. Janes. 1University College London, London, UK, 2North Middlesex University Hospital, London, UK, 3The Whittington Hospital, London, UK

Introduction Transbronchial lung biopsies (TBLBs) and endobronchial biopsies (EBBs) are standard techniques for the diagnosis of pulmonary sarcoidosis with yields of up to 75%. Cohort studies suggest endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) may be a useful tool for the diagnosis of sarcoidosis. However, no data are currently available on the safety and efficacy of combining standard bronchoscopic techniques with EBUS-TBNA. A prospective study was therefore carried out to evaluate the diagnostic yield from EBUS-TBNA, TBLB, EBB and their combination in patients with suspected sarcoidosis, for whom pathological confirmation was clinically required.

Methods Patients with enlarged mediastinal lymph nodes and suspected sarcoidosis (stages 1 and 2) underwent EBUS-TBNA. In all patients the EBUS scope was withdrawn and replaced with a standard videobronchoscope under conscious sedation and TBLB and EBB were performed.

Results Twenty-seven patients with suspected sarcoidosis underwent EBUS-TBNA and bronchoscopy. Overall 16 patients were diagnosed with sarcoidosis, 7 had tuberculosis, 2 had reactive lymphadenopathy, 1 had lymphoma (diagnosed on EBUS-TBNA) and 1 remains in follow-up. The sensitivity of EBUS-TBNA for obtaining non-caseating granulomas in patients with sarcoidosis was 81%. The sensitivity of standard bronchoscopic techniques alone was significantly lower at 44% (p = 0.029). Yield per procedure according to stage of sarcoidosis is summarised in table 1. In patients with negative EBUS-TBNA, non-caseating granulomas were obtained by TBLB of radiologically normal lung parenchyma in one patient and EBB of normal endobronchial mucosa in one patient. The sensitivity of combined EBUS and standard bronchoscopic techniques was 94%. No major complications related to EBUS-TBNA or sedation were observed. One patient undergoing TBLB experienced a pneumothorax, requiring admission but not intercostal drainage.

Conclusion Combining EBUS-TBNA with standard bronchoscopic techniques is a safe procedure and optimises the diagnostic yield in patients with pulmonary sarcoidosis. Further prospective studies with economic analyses are warranted to determine whether the combination of EBUS-TBNA with standard bronchoscopic techniques can avoid mediastinoscopies in patients with suspected sarcoidosis for whom pathological confirmation is required.

Abstract S103 Table 1

Diagnostic yield of EBUS-TBNA and bronchoscopy according to stage of sarcoidosis


J. Alçada, N. Navani, H. L. Booth, S. M. Janes, J. George. Department of Thoracic Medicine, University College Hospital, London, UK

Introduction and Objectives The use of self-expanding metallic stents (SEMS) in the management of large airway obstruction and sealing of fistulae has become more established with the advent of removable stents. As a tertiary centre we have significant experience in the insertion of airway stents. We report our experience and evaluate the clinical efficacy and safety of removable SEMS.

Methods We conducted a retrospective study between January 2005 and July 2009. Data analysis was carried out using SPSS.

Results 36 stents were inserted in a total of 33 patients (20 males and 13 females). The mean age was 59.7±14.4 years (range 22–81). 32 stents (84.2%) were deployed for malignant conditions and 4 (10.5%) for benign diseases. 81.8% of patients had malignant airway obstruction and 6.1% had tracheo-oesophageal fistulae. Obstruction was located to the trachea in 44.4% of cases. 88.9% of patients reported improvement in symptoms in the first 24 h. 62.9% of patients were in severe respiratory distress prior to SEMS insertion, with immediate improvement thereafter. Complications were reported in 14 stents, with 2 presenting within 24 h. We recorded 1 case of stent fracture, 6 cases of migration, 5 cases of mucus plugging, 1 minor bronchial tear associated with stent placement, and 1 case of stent-associated respiratory tract infection. 12 stents were easily removed, with no associated complications. 17 deaths were reported, none related to stent insertion and all were in patients with advanced malignant disease. Survival for these patients ranged from 7 to 430 days poststent insertion.

Conclusions SEMS provide an effective, safe and feasible therapeutic modality in patients with benign and malignant airway stenoses. Although associated with significant complications, they have the advantage of providing immediate relief from breathlessness and imminent asphyxia. In patients with malignancy, SEMS enable definitive oncological treatment to be given electively, and in greater safety, and are easily removed after completion of treatment.

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