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I A Du Rand,
P V Barber,
J Goldring,
R A Lewis,
S Mandal,
M Munavvar,
R C Rintoul, P L Shah,
S Singh,
M G Slade,
A Woolley
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ABSTRACT: This new guideline covers the rapidly advancing field of interventional bronchoscopy using flexible bronchoscopy. It includes the use of more complex diagnostic procedures such as endobronchial ultrasound, interventions for the relief of central airway obstruction due to malignancy and the recent development of endobronchial therapies for chronic obstructive pulmonary disease and asthma. The guideline aims to help all those who undertake flexible bronchoscopy to understand more about this important area. It also aims to inform respiratory physicians and other specialists dealing with lung cancer of the procedures possible in the management and palliation of central airway obstruction. The guideline covers transbronchial needle aspiration and endobronchial ultrasound-guided transbronchial needle aspiration, electrocautery/diathermy, argon plasma coagulation and thermal laser, cryotherapy, cryoextraction, photodynamic therapy, brachytherapy, tracheobronchial stenting, electromagnetic navigation bronchoscopy, endobronchial valves for emphysema and bronchial thermoplasty for asthma.
Thorax 11/2011; 66(11):1014-5. · 6.84 Impact Factor
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I A Du Rand,
P V Barber,
J Goldring,
R A Lewis,
S Mandal,
M Munavvar,
R C Rintoul, P L Shah,
S Singh,
M G Slade,
A Woolley
Thorax 11/2011; 66 Suppl 3:iii1-21. · 6.84 Impact Factor
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P L Shah,
D-J Slebos,
P F G Cardoso,
E Cetti,
K Voelker,
B Levine,
M E Russell,
J Goldin,
M Brown,
J D Cooper,
G W Sybrecht
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ABSTRACT: Airway bypass is a bronchoscopic lung-volume reduction procedure for emphysema whereby transbronchial passages into the lung are created to release trapped air, supported with paclitaxel-coated stents to ease the mechanics of breathing. The aim of the EASE (Exhale airway stents for emphysema) trial was to evaluate safety and efficacy of airway bypass in people with severe homogeneous emphysema.
We undertook a randomised, double-blind, sham-controlled study in 38 specialist respiratory centres worldwide. We recruited 315 patients who had severe hyperinflation (ratio of residual volume [RV] to total lung capacity of ≥0·65). By computer using a random number generator, we randomly allocated participants (in a 2:1 ratio) to either airway bypass (n=208) or sham control (107). We divided investigators into team A (masked), who completed pre-procedure and post-procedure assessments, and team B (unmasked), who only did bronchoscopies without further interaction with patients. Participants were followed up for 12 months. The 6-month co-primary efficacy endpoint required 12% or greater improvement in forced vital capacity (FVC) and 1 point or greater decrease in the modified Medical Research Council dyspnoea score from baseline. The composite primary safety endpoint incorporated five severe adverse events. We did Bayesian analysis to show the posterior probability that airway bypass was superior to sham control (success threshold, 0·965). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00391612.
All recruited patients were included in the analysis. At 6 months, no difference between treatment arms was noted with respect to the co-primary efficacy endpoint (30 of 208 for airway bypass vs 12 of 107 for sham control; posterior probability 0·749, below the Bayesian success threshold of 0·965). The 6-month composite primary safety endpoint was 14·4% (30 of 208) for airway bypass versus 11·2% (12 of 107) for sham control (judged non-inferior, with a posterior probability of 1·00 [Bayesian success threshold >0·95]).
Although our findings showed safety and transient improvements, no sustainable benefit was recorded with airway bypass in patients with severe homogeneous emphysema.
Broncus Technologies.
The Lancet 09/2011; 378(9795):997-1005. · 38.28 Impact Factor
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ABSTRACT: Bronchoscopic therapies to reduce lung volumes in chronic obstructive pulmonary disease are intended to avoid the risks associated with lung volume reduction surgery (LVRS) or to be used in patient groups in whom LVRS is not appropriate. Bronchoscopic lung volume reduction (BLVR) using endobronchial valves to target unilateral lobar occlusion can improve lung function and exercise capacity in patients with emphysema. The benefit is most pronounced in, though not confined to, patients where lobar atelectasis has occurred. Few data exist on their long-term outcome. 19 patients (16 males; mean±sd forced expiratory volume in 1 s 28.4±11.9% predicted) underwent BLVR between July 2002 and February 2004. Radiological atelectasis was observed in five patients. Survival data was available for all patients up to February 2010. None of the patients in whom atelectasis occurred died during follow-up, whereas eight out of 14 in the nonatelectasis group died (Chi-squared p=0.026). There was no significant difference between the groups at baseline in lung function, quality of life, exacerbation rate, exercise capacity (shuttle walk test or cycle ergometry) or computed tomography appearances, although body mass index was significantly higher in the atelectasis group (21.6±2.9 versus 28.4±2.9 kg·m(-2); p<0.001). The data in the present study suggest that atelectasis following BLVR is associated with a survival benefit that is not explained by baseline differences.
European Respiratory Journal 06/2011; 37(6):1346-51. · 5.89 Impact Factor
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Thorax 09/2010; · 6.84 Impact Factor
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ABSTRACT: The assessment of medical trainees is becoming an increasingly prominent issue, with current methods having varying degrees of inherent subjectivity and bias. Cusum analysis is a technique used in quality control systems, and is starting to be employed in medical training. Endobronchial ultrasound (EBUS) is an established tool in the diagnosis and staging of lung cancer, although its use in the UK is currently restricted. As it becomes more widespread, there will be a need to assess trainees' competence accurately to ensure that those performing EBUS at new centres are appropriately skilled.
A retrospective review of clinical practice in tertiary referral centres in England, Scotland and Spain was carried out. The study group comprised 500 patients undergoing EBUS for the diagnosis and staging of lung cancer as part of a clinical service. Using cusum analysis, the first 100 cases from each of the five centres are presented. Each centre has one consultant physician as the primary EBUS operator, and all operators began using EBUS at their current centre (ie, no learning from prior experience). The data are presented as learning curves.
It is evident that there is a wide range of time over which EBUS-guided transbronchial needle aspiration (TBNA) competence is attained. The pooled sensitivity was 67.4% (individual sensitivities 66.7, 70.7, 61.2, 80.3 and 59.7%).
Cusum analysis is well suited to the assessment of procedures with a binary outcome, but accurate and appropriate standards of practice must be determined prior to assessment to ensure correct identification of underperformance. This report suggests that the learning curve for EBUS is greater than previously reported using different methods, and that even experienced bronchoscopists vary in their speed of learning.
Thorax 06/2010; 65(6):534-8. · 6.84 Impact Factor
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ABSTRACT: Multiplex protein technology has the potential to identify biomarkers for the differentiation, classification and improved understanding of the pathogenesis of interstitial lung disease. The aim of this study was to determine whether a 30-inflammatory biomarker panel could discriminate between healthy controls, sarcoidosis and systemic sclerosis (SSc) patients independently of other clinical indicators. We also evaluated whether a panel of biomarkers could differentiate between the presence or absence of lung fibrosis in SSc patients. We measured 30 circulating biomarkers in 20 SSc patients, 21 sarcoidosis patients and 20 healthy controls using Luminex bead technology and used Fisher's discriminant function analysis to establish the groups of classification mediators. There were significant differences in median concentration measurements between study groups for 20 of the mediators but with considerable range overlap between the groups, limiting group differentiation by single analyte measurements. However, a 17-analyte biomarker model correctly classified 90% of study individuals to their respective group and another 14-biomarker panel correctly identified the presence of lung fibrosis in SSc patients. These findings, if they are corroborated by independent studies in other centres, have potential for clinical application and may generate novel insights into the modulation of immune profiles during disease evolution.
European Respiratory Journal 07/2009; 34(6):1376-82. · 5.89 Impact Factor
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Thorax 04/2005; 60(3):180-1. · 6.84 Impact Factor
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ABSTRACT: Exhaled nitric oxide (ENO), a marker of inflammation in airway diseases is decreased in cystic fibrosis (CF) patients, perhaps because nitric oxide (NO) is metabolized to oxidative end-products. A stable product, 3-nitrotyrosine, may indicate local formation of reactive nitrogen species. Whether NO metabolites in exhaled breath condensate may be increased in CF patients was investigated. The fractional concentration of ENO (Feno), nitrotyrosine and oxides of nitrogen in exhaled breath condensate from 36 stable CF patients were compared to 14 normal subjects using an enzyme immunoassay and fluorescence assay. Nitrotyrosine levels in breath condensate were increased significantly in stable CF patients, compared with normal subjects (25.3 +/- 1.5 versus 6.3 +/- 0.8 ng x mL(-1), p<0.0001). There was an inverse correlation between the levels of nitrotyrosine and the severity of lung disease. Feno levels were significantly lower in CF patients than in normal subjects (4.4 +/- 0.3 versus 5.6 +/- 0.4 (parts per billion), p<0.05). No correlation was found between nitrotyrosine and Feno levels in CF. There was no significant difference in the levels of nitrite and nitrate between CF patients and normals. The elevation in nitrotyrosine may reflect increased formation of reactive nitrogen species such as peroxynitrite or direct nitration by granulocyte peroxidases, indicating increased oxidative stress in airways of cystic fibrosis patients.
European Respiratory Journal 06/2001; 17(6):1201-7. · 5.89 Impact Factor
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ABSTRACT: Chronic endobronchial sepsis and profuse airway secretions dominate pulmonary disease in cystic fibrosis. Recombinant human DNase I (dornase alfa) reduces the viscoelasticity of airway secretions and hence may improve clearance of airway secretions.
To evaluate the long-term influence of dornase alfa on disease progression by performing a case-controlled study with dornase alfa over a period of 4 years.
A cohort of patients with cystic fibrosis who have been treated with dornase alfa were matched with a control group of patients with cystic fibrosis who had not received treatment with dornase alfa. The patients were matched by pulmonary function, age, and then sex. All available measurements of forced expiratory volume in one second (FEV1), height, weight and sputum bacteriology were collected for periods when the patients were free from respiratory exacerbations.
Thirty-eight patients were matched. Slopes of median changes in FEV1 were -2.19 (-3.32, -1.06) in the control group and -0.75 (-1.87, 0.36) in the dornase alfa-treated group (p = 0.076). There were more infective exacerbations per patient year in the control group [3.13 (1.25-4.25)] in comparison to the dornase alfa group [1.25 (0.63-3.0), p = 0.035] over the 4-year treatment period. Antibiotic requirements were also greater with a median 43.75 (17.5-60.0) days of intravenous antibiotic use per patient year in the control group and 16.25 (8.5-44.0) days in the dornase alfa group (p = 0.034).
The trends suggest that dornase alfa may have some influence on disease progression but in view of the limitations of the current study the need for further long-term studies in larger cohorts of patients is emphasised.
Respiration 02/2001; 68(2):160-4. · 2.26 Impact Factor
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ABSTRACT: Ethane is produced from lipid peroxidation and can be measured in the exhaled air. Cystic fibrosis (CF) is characterized by recurrent respiratory infections, release of reactive oxygen species by inflammatory cells, and increased oxidative stress. We measured exhaled ethane in 23 CF subjects (mean age +/- SEM, 21 +/- 4 yr; 10 male, FEV(1) 62 +/- 4%) and compared it with two other noninvasive markers of oxidative stress and inflammation, carbon monoxide (CO) and nitric oxide (NO). Exhaled ethane was collected during a flow and pressure-controlled exhalation into a reservoir discarding dead space air contaminated with ambient air. A sample (2 ml) of the expired air was analyzed by chromatography. Ethane levels were elevated in patients not on steroids (n = 13, 1.99 +/- 0.20 ppb) compared with steroid-treated patients (n = 10, 0.67 +/- 0.09 ppb, p < 0.01) and with 14 nonsmoking control (8 men, age 33 +/- 2.8 yr) subjects (0.82 +/- 0.40 ppb, p < 0.05). In patients not on steroid treatment ethane was correlated to airway obstruction as assessed by the ratio of residual volume to total lung capacity (RV/ TLC) (r = 0. 66, p < 0.05) and exhaled CO (r = 0.65, p < 0.05). CO concentrations were also higher in patients not on steroid treatment (3.4 +/- 0.2 ppm) than in steroid-treated patients (2.6 +/- 0.1 ppm, p < 0.05), whereas NO concentrations were not influenced by steroid treatment (3.0 +/- 0.4 ppm and 2.9 +/- 0.2 ppm, p > 0.05) and were lower than in a control group (7.0 +/- 0.4 ppb, p < 0.05). Exhaled ethane is elevated in CF, reduced in steroid-treated patients and correlates with CO and RV/TLC; therefore, it may be a useful noninvasive marker of oxidative stress.
American Journal of Respiratory and Critical Care Medicine 04/2000; 161(4 Pt 1):1247-51. · 11.08 Impact Factor
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ABSTRACT: Staphylococcus aureus is an uncommon pathogen in bronchiectasis not caused by cystic fibrosis (CF). The object of this study was to identify characteristics that cause patients to be prone to infection with S. aureus. The study population consisted of patients with bronchiectasis attending the authors' unit, excluding those with a diagnosis of overt CF. All patients had a high resolution computer tomographic scan (HRCT) of the thorax which demonstrated bronchiectasis. Cases that were currently chronically infected with S. aureus (isolated consecutively on more than two occasions >3 months apart) were identified (n = 12) and compared with 74 control patients who had not been chronically infected with S. aureus. Patients were carefully evaluated to determine the aetiology of their disease. Odds ratios (OR) and 95% confidence intervals (CI) as measures of the association between disease characteristics and chronic infection with S. aureus were calculated. The results for patients chronically infected by S. aureus demonstrated significant associations with allergic bronchopulmonary aspergillosis (ABPA; OR = 8.8, 95% CI 1.8-41.9), atypical variants of CF (OR = 12.0, 95% CI 1.8-81.7) or equivocal sweat sodium values (OR = 4.0, 95% CI 1.0-15.3). The associations persisted when the analysis was based on cases (n = 28) in whom S. aureus had ever been isolated from sputum. In the latter analysis there was also a significant association with predominant upper zone disease on HRCT. These results suggest that patients with bronchiectasis in whom S. aureus is isolated from sputum should be carefully evaluated to exclude allergic bronchopulmonary aspergillosis or atypical cystic fibrosis.
European Respiratory Journal 12/1999; 14(6):1340-4. · 5.89 Impact Factor
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ABSTRACT: Inflammation, oxidative stress, and recurrent pulmonary infections are major aggravating factors in cystic fibrosis. Nitric oxide (NO), a marker of inflammation, is not increased, however, probably because it is metabolised to peroxynitrite. Exhaled carbon monoxide (CO), a product of heme degradation by heme oxygenase 1 (HO-1) which is induced by inflammatory cytokines and oxidants, was therefore tested as a non-invasive marker of airway inflammation and oxidative stress.
Exhaled CO and NO concentrations were measured in 29 patients (15 men) with cystic fibrosis of mean (SD) age 25 (1) years, forced expiratory volume in one second (FEV(1)) 43 (6)%, 14 of whom were receiving steroid treatment.
The concentration of exhaled CO was higher in patients with cystic fibrosis (6.7 (0.6) ppm) than in 15 healthy subjects (eight men) aged 31 (3) years (2.4 (0.4) ppm, mean difference 4.3 (95% CI 2.3 to 6.1), p<0.001). Patients not receiving steroid treatment had higher CO levels (8.4 (1.0) ppm) than treated patients (5.1 (0.5) ppm, mean difference 3.3 (95% CI -5.7 to -0.9), p<0.01). Normal subjects had higher NO levels (6.8 (0.4) ppb) than patients with cystic fibrosis (3.2 (0.2) ppb, mean difference 3.8 (95% CI 2.6 to 4.9), p<0.05) and were not influenced by steroid treatment (3.8 (0.4) ppb and 2.7 (0. 3) ppb for treated and untreated patients, respectively, mean difference 0.8 (95% CI -0.6 to 2.3), p>0.05). Patients homozygous for the DeltaF508 CFTR mutation had higher CO and NO concentrations than heterozygous patients (CO: 7.7 (1.8) ppm and 4.0 (0.6) ppm, respectively, mean difference 3.7 (95% CI -7.1 to -0.3), p<0.05; NO: 4.1 (0.5) ppb and 1.9 (0.7) ppb, respectively, mean difference 2.2 (95% CI -3.7 to -0.6), p<0.05).
High exhaled CO concentrations in patients with cystic fibrosis may reflect induction of HO-1. Measurement of exhaled CO concentrations may be clinically useful in the management and monitoring of oxidation and inflammatory mediated lung injury.
Thorax 11/1999; 54(10):917-20. · 6.84 Impact Factor
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P L Shah
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ABSTRACT: Cystic fibrosis is a genetic disease that affects one in 2500 live births. A basic defect in chloride transport leads to impaired clearance of airway secretions and a susceptibility to bacterial infection. Once infection is established there is a vicious cycle that leads to progressive inflammation and infection. Although cystic fibrosis is a multisystem disorder, pulmonary disease is the main cause of morbidity and respiratory failure remains the main cause of death. This review discusses the strategies for treating pulmonary disease in patients with cystic fibrosis and focuses on some of the therapeutic developments.
IDrugs: the investigational drugs journal 08/1999; 2(7):694-701. · 2.28 Impact Factor
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The Lancet 06/1999; 353(9166):1727. · 38.28 Impact Factor
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P L Shah
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ABSTRACT: Cystic fibrosis (CF) is a genetic disease where abnormalities in ion transport lead to poor clearance of viscoelastic secretions and a susceptibility to bacterial colonisation. Once established the infection/inflammatory cascade appears to be self-perpetuating. Treatment is therefore based on a number of strategies. Recently, advances have been concentrated at correcting the gene defect. Other strategies include correction of the ion transport defect. These may be crucial in patients if started before there is significant pulmonary disease. Developments aimed at improving the rheological properties of secretions, controlling airway infection and inflammation are essential once bronchopulmonary sepsis is established. This report looks at some of the clinical trials that are ongoing or planned in the treatment of pulmonary disease in CF.
Expert Opinion on Investigational Drugs 02/1998; 7(1):91-8. · 5.27 Impact Factor
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ABSTRACT: Cystic fibrosis is characterised by chronic bronchopulmonary sepsis. Various therapeutic modalities attempt to enhance the clearance of airway secretions. Dornase alfa (recombinant human deoxyribonuclease) reduces the viscoelasticity of sputum from patients with cystic fibrosis by depolymerising extracellular DNA. The drug is administered as an aerosol using a jet nebuliser at a dosage of 2.5mg once daily. It improves pulmonary function and reduces the risk of respiratory exacerbations requiring parenteral antibacterials. Various clinical trials have demonstrated a heterogeneous response to dornase alfa and have been unable to predict which groups of patients benefit from treatment. Patient selection is further complicated because some individuals do not exhibit improvements in lung function, but benefit in terms of a decrease in infective exacerbations. All patients with cystic fibrosis who produce purulent sputum are potential candidates for dornase alfa therapy. We suggest that compliant patients be considered for treatment with dornase alfa, irrespective of disease severity, but should be closely monitored and be assessed at regular intervals to monitor treatment response.
BioDrugs 01/1998; 8(6):439-45. · 3.44 Impact Factor
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ABSTRACT: The poor clearance of airway secretions in patients with cystic fibrosis perpetuates the chronic bronchopulmonary sepsis that is predominant. In recent years, novel drugs have been developed to alter the rheologic properties of the secretions in an attempt to improve airway clearance. Dornase alfa reduces the viscoelasticity of sputum from patients with cystic fibrosis and may enhance the clearance of secretions. Current clinical knowledge suggests that it is a safe treatment that improves pulmonary function and reduces respiratory exacerbations. The response, however, is heterogeneous and unpredictable. Scientific studies support the therapeutic rationale for the use of dornase alfa in that treatment reduces the viscoelasticity of airway secretions. Its effect on bacterial persistence and airway inflammation, however, is marginal. The key piece of information that would influence the long-term use of dornase alfa is how it affects disease progression, and at present this is unknown.
Current opinion in pulmonary medicine 12/1997; 3(6):410-3. · 3.08 Impact Factor
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ABSTRACT: Increasingly, proteins are delivered to the respiratory tract as an aerosol, and clinical efficacy is dependent on optimal delivery of the protein in an intact form. The object of this study was to compare the in vivo and in vitro results of two aerosol delivery systems for the aerosolization of recombinant human deoxyribonuclease I (rhDNase) in patients with cystic fibrosis (CF). Patients with CF who were to be initiated on rhDNase were randomized either to the Hudson nebulizer and Pulmo-Aide compressor or to the Sidestream nebulizer driven by the CR50 air compressor. An in vitro study was performed in six sets of the two aerosol delivery systems. One hundred and seventy three patients were randomized in this open study, where rhDNase was administered for 7 days. Improvements in pulmonary function were observed in both groups following 1 week of therapy with rhDNase. Changes in the Sidestream/CR50 and Hudson/Pulmo-Aide groups, respectively, were: 16 and 11% for forced expiratory volume in one second (p=0.14); 12 and 10% for forced vital capacity (p=0.70); and 14 and 7% for forced expiratory flow at 25-75% of expiration (FEF(25-75)) (p=0.18). A greater proportion of patients in the Sidestream/CR50 group (58%) had a >10% response in FEF(25-75) compared to the Hudson/Pulmo-Aide group (42%; p=0.03). The Sidestream nebulizer had a faster nebulization rate (p<0.05), lower mass median diameter for the aerosol mass produced (p<0.001), higher percentage of particles in the respirable range (p<0.001) and greater respirable output (p<0.005), compared to the Hudson nebulizer. The Sidestream/CR50 combination is a quicker, more efficient system in vitro than the Hudson/Pulmo-Aide combination, whereas the in vivo study only suggested a difference. Clinically, the two systems have similar efficacy.
European Respiratory Journal 06/1997; 10(6):1261-6. · 5.89 Impact Factor
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ABSTRACT: Cystic fibrosis (CF) is the commonest inherited disease of the Caucasian population, with a high morbidity and mortality from pulmonary disease. The high viscoelasticity of CF sputum is due, in part, to the high deoxyribonucleic acid (DNA) content. Recombinant human deoxyribonuclease I (rhDNase) has been developed and in vitro studies have shown that it reduces the viscoelasticity of CF sputum. This article reviews the in vivo clinical studies conducted to determine the safety and efficacy of rhDNase in the treatment of pulmonary disease in CF. Initial Phase I studies showed preliminary safety and some evidence of clinical benefit. Subsequently, two Phase II studies were conducted in the US and UK during which patients received rhDNase for 10 days. A Phase III study of 24 weeks duration involving 968 patients in 51 centres in North America is also reported in detail. Longer term open-label studies, the results of intermittent administration, administration to severely ill patients and the use of different delivery systems are reviewed. The Phase II study reported improvements in pulmonary function and had a good safety profile. The Phase III study showed improvement in forced expiratory volume in one second (FEV1) of 5.8 and 5.6% in patients treated once and twice daily, respectively. The risk of developing an exacerbation was reduced by 28% with once daily treatment and 37% with twice daily treatment compared to placebo. The drug was safe and there was some improvement in quality of life data. Recombinant human deoxyribonuclease is a new therapy for pulmonary disease in cystic fibrosis which has been shown to benefit patients when used in conjunction with conventional therapy.
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo 05/1996; 51(2):125-9.
