Targeted lung denervation for moderate to severe COPD: a pilot study.

BACKGROUND: Parasympathetic pulmonary nerves release acetylcholine that induces smooth muscle constriction. Disruption of parasympathetic pulmonary nerves improves lung function and COPD symptoms. AIMS: To evaluate 'targeted lung denervation' (TLD), a novel bronchoscopic therapy based on ablation of parasympathetic pulmonary nerves surrounding the main bronchi, as a potential therapy for COPD. METHODS: This 1-year, prospective, multicentre study evaluated TLD in patients with COPD forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (FEV1/FVC <0.70; FEV1 30%-60% predicted). Patients underwent staged TLD at 20 watts (W) or 15 W following baseline assessment off bronchodilators. Assessments were repeated on tiotropium before treatment and off bronchodilators at 30, 90, 180, 270 and 365 days after TLD. The primary endpoint was freedom from documented and sustained worsening of COPD directly attributable to TLD to 1 year. Secondary endpoints included technical feasibility, change in pulmonary function, exercise capacity, and quality of life. RESULTS: Twenty-two patients were included (n=12 at 20 W, n=10 at 15 W). The procedures were technically feasible 93% of the time. Primary safety endpoint was achieved in 95%. Asymptomatic bronchial wall effects were observed in 3 patients at 20 W. The clinical safety profiles were similar between the two energy doses. At 1 year, changes from baseline in the 20 W dose compared to the 15 W dose were: FEV1 (+11.6%±32.3 vs +0.02%±15.1, p=0.324), submaximal cycle endurance (+6.8 min±12.8 vs 2.6 min±8.7, p=0.277), and St George's Respiratory Questionnaire (-11.1 points ±9.1 vs -0.9 points ±8.6, p=0.044). CONCLUSIONS: Bronchoscopic TLD, based on the concept of ablating parasympathetic pulmonary nerves, was feasible, safe, and well tolerated. Further investigation of this novel therapy is warranted. TRIAL REGISTRATION NUMBER: NCT01483534.

Endobronchial valves in the management of recurrent haemoptysis.

Minimally invasive treatment modalities for life-threatening haemoptysis in patients unresponsive to medical interventions and/or in patients deemed functionally inoperable are limited. We describe the implantation of endobronchial valves in a patient with recurrent haemoptysis, which presents both a novel indication for the use of these devices and a novel intervention for haemoptysis. Our patient is a 30-year-old male who developed bilateral upper lobe aspergillomata following previous pulmonary tuberculosis. The patient had a history of multiple hospitalisations for life-threating haemoptysis despite repeated bronchial artery embolisations. He was deemed to be inoperable given the bilateral nature of his disease and very poor pulmonary reserves. We proceeded to identify the segments involved with the aid of computed tomography reconstruction and implanted 3 endobronchial valves. Our patient remained haemoptysis free for 6 months and experienced no stent-related complications. Moreover, he was subsequently employed as a manual labourer and showed significant improvements in his functional capacity. Endobronchial valves may therefore represent a viable medium-term treatment option as a blockade device in patients unresponsive to medical interventions and/or in patients deemed functionally inoperable. Prospective studies are indicated to better delineate the role of endobronchial valves in this setting.

The yield of different pleural fluid volumes for Mycobacterium tuberculosis culture.

We prospectively compared the culture yields of two pleural fluid volumes (5 and 100 ml) inoculated in liquid culture medium in 77 patients of whom 58 (75.3%) were diagnosed with pleural tuberculosis. The overall fluid culture yield was high (60.3% of cases with pleural tuberculosis). The larger volume had a faster time to positivity (329 vs 376 h, p=0.055) but its yield was not significantly higher (53.5% vs 50%; p=0.75). HIV-positive patients were more likely to have positive cultures (78.9% vs 51.5%; p=0.002).

Bronchoscopic treatment of emphysema: state of the art.

In recent years, different bronchoscopic techniques have been proposed for the treatment of emphysema, with the aim of obtaining the same clinical and functional advantages of lung volume reduction surgical techniques while reducing risks and costs. Such techniques can be classified into: methods employing devices that block the airways (e.g. spigots and unidirectional valves), methods that have a direct effect on the lung parenchyma (polymeric lung volume reduction, coils and thermal vapor ablation) and procedures that facilitate the expiration of trapped air from the emphysematous lung (airway bypass). This review aimed to evaluate the indications, outcomes and safety of the different techniques, based on the evidence from the available literature. Results obtained by these methods are encouraging, but they are still based mainly on studies with small groups of patients. However, several trials are ongoing and in the near future we will acquire more knowledge which should lead to a better optimization of these procedures. Meanwhile, the bronchoscopic treatment of emphysema cannot yet be considered a standard of care and patients should be treated in the context of clinical trials or controlled registries, with well-defined programs of evaluation and follow-up.

Transthoracic ultrasonography for the respiratory physician.

Transthoracic ultrasonography is still not utilized to its full potential by respiratory physicians, despite being a well-established and validated imaging modality. It allows for an immediate and mobile assessment that can potentially augment the physical examination of the chest. Ultrasound (US)-assisted procedures can be performed by a single clinician with no sedation and with minimal monitoring, even outside of theatre. The main indications for the use of transthoracic US are: the qualitative and quantitative description of pleural effusions, pleural thickening, diaphragmatic dysfunction and chest-wall and pleural tumours. It may also be used to visualise lung tumours and other parenchymal pulmonary processes provided they abut the pleura. It is at least as sensitive as chest radiographs as far as the detection of a pneumothorax is concerned. It is the ideal tool to assist with thoracocentesis and drainage of effusions. The US-assisted fine-needle aspiration and/or cutting-needle biopsy of extrathoracic lymph nodes, lesions arising from the chest wall, pleura, peripheral lung and mediastinum, are safe and have a high yield in the hands of chest physicians. US may also guide the aspiration and biopsy of diffuse pulmonary infiltrates, consolidations and lung abscesses, provided the chest wall is abutted. Advanced applications of transthoracic US include the diagnosis of pulmonary embolism.

Speed of ascent during stair climbing identifies operable lung resection candidates.

BACKGROUND: Preoperative evaluation of lung resection candidates with impaired pulmonary reserves includes measurement of aerobic capacity. Stair climbing is an attractive low-cost alternative to treadmill exercise testing but it lacks standardisation. OBJECTIVES: To directly compare stair climbing and treadmill exercise testing with respect to an established cut-off value for lung resection. METHODS: We subjected 56 lung resection candidates to both symptom-limited treadmill exercise testing and stair climbing to a maximum of 20 m. Both exercise tests were monitored with the same portable spiroergometer. Subjects were on average 46.6 years old, 61% were male and 54% had FEV(1)/FVC < 70%. Mean FEV(1) and DLCO(c) were 51.6 and 57.1%, respectively. RESULTS: Mean altitude reached, exercise time, speed of ascent and peak VO(2) were 16.9 m, 74 s, 14.7 m/min and 22.4 ml/min/kg, respectively, in 54 subjects completing stair climbing. Thirty-one subjects (58%) reached 20 m without stopping. Treadmill tests were completed by 51 subjects and lasted longer (432 s; p < 0.001), but VO(2max) was not different compared to stair climbing (22.7 ml/min/kg; p = 0.673). Speed of ascent was significantly correlated to both stair climbing peak VO(2) (r = 0.63) and treadmill VO(2max) (r = 0.67). All 19 subjects (34%) who reached 20 m in 80 s or less (≥15 m/min) had a VO(2max) of ≥20 ml/min/kg. CONCLUSIONS: We found a clinically useful correlation between speed of ascent during stair climbing and VO(2max) during treadmill exercise testing. Climbing to 20 m with an average speed of ascent of ≥15 m/min accurately identified subjects qualifying for pneumonectomy according to established criteria.

Blood loss during flexible bronchoscopy: a prospective observational study.

BACKGROUND: Haemorrhage remains a complication of flexible bronchoscopy. OBJECTIVES: We aimed to measure the actual blood loss in patients at low risk of bleeding and to assess its association with the underlying pulmonary pathology, superior vena cava (SVC) syndrome, procedure(s) performed and laboratory values. METHODS: We screened all patients scheduled for flexible bronchoscopy and enrolled 234 subjects over 18 months. Subjects with a history of haemorrhagic tendency, platelets <20 × 10(3)/µl, a history of anti-coagulation or anti-platelet therapy and a history or clinical evidence of liver failure were excluded. Blood loss during the procedure was measured from aspirated secretions with a haemoglobin detector and categorised into minimal (<5 ml), mild (5-20 ml), moderate (20-100 ml) and severe bleeding (>100 ml). RESULTS: Overall, 210 subjects had minimal, 19 had mild and 5 had moderate bleeding. No subject experienced severe blood loss. Patients with SVC syndrome had the highest mean blood loss (6.0 ml) when compared to bronchogenic carcinoma without SVC syndrome (p = 0.033) and other diagnosis (p = 0.026). The blood loss with trans-bronchial needle aspiration (TBNA, mean 3.4 ml) was significantly less than with TBNA combined with endobronchial or transbronchial biopsy (mean 5.0 ml, p < 0.001). Anaemia, a platelet count of 25-155 × 10(3)/µl and an international normalized ratio of >1.3 were not associated with an increased risk of bleeding. CONCLUSIONS: We found no severe bleeding in this cohort preselected to have a low clinical risk of bleeding. Moreover, our data suggest that clinical screening and a platelet count ≥20 × 10(3)/µl alone may be sufficient to identify low-risk patients.

Smoking prevention and cessation in the Africa and Middle East region: a consensus draft guideline for healthcare providers--executive summary.

Despite the abundance of scientific evidence confirming the health consequences of smoking and other forms of tobacco use, the tobacco epidemic remains an important public health problem and by 2030 it is predicted that more than 80% of tobacco deaths will be in developing countries. In Africa and the Middle East, many local factors contribute to the initiation and maintenance of tobacco use. Although efforts to reduce the mortality and morbidity associated with smoking and tobacco dependence are underway, there is a need for guidance on how to utilize appropriate tobacco control policies and psychology- and pharmacology-based therapies to counter tobacco dependence as recommended by the Framework Convention on Tobacco Control (FCTC). A group of tobacco cessation experts from public health services and/or academic institutions in Africa and the Middle East participated in a series of four meetings held in Cairo, Cape Town, and Dubai between May 2008 and February 2011 to develop a draft guideline tailored to their region. This article provides the background to the development of this draft smoking cessation guideline and discusses how the recommendations can be implemented and progress monitored to promote both primary prevention and cessation of tobacco use within our countries. The draft guideline for Africa and the Middle East provides an important resource in combating the devastating effects of tobacco use in these regions which can be further localized through engagement with local stakeholders in the countries of the region.

Immunochemistry and lung cancer: application in diagnosis, prognosis and targeted therapy.

Immunochemistry is now an established ancillary technique in lung cancer diagnosis. Not only does it help in supporting the morphological diagnosis of malignancy, but its role now extends to the determination of cell lineage, ascertaining the primary site of tumour origin and contributing to decisions on prognosis and treatment. Early detection and confirmation of lung cancer facilitate early treatment decisions. Lung cancer management now has a multidisciplinary approach which includes cytopathologists and clinicians. Some clinicians may not understand what immunochemistry is and what its role is in lung cancer diagnosis, prognosis and therapy. The purpose of this paper is to define immunochemistry, on the background of basic respiratory airway epithelial structure and cancer biology, and discuss its application in the diagnosis, treatment and determination of prognosis of lung cancer.

The diagnostic yield and safety of ultrasound-assisted transthoracic fine-needle aspiration of drowned lung.

BACKGROUND: Proximal lung tumors, though not discernable by means of transthoracic ultrasound (US), may cause varying degrees of pulmonary collapse and postobstructive pneumonitis which may give rise to a 'drowned lung' appearance on chest computed tomography (CT) and US. The diagnostic yield for malignancy of US-assisted transthoracic fine-needle aspiration (FNA) of these areas of drowned lung is unknown. OBJECTIVES: We aimed to explore the feasibility of US-assisted FNA in this setting by prospectively investigating its diagnostic yield and safety. METHODS: We enrolled 31 patients (aged 59.4 ± 9.7 years, 17 males) with central tumors and secondary drowned lung on CT scan. A respiratory physician performed transthoracic US to identify the target drowned lung tissue. Three US-assisted superficial FNA passes (≤20 mm from the pleura) were followed by 3 deeper FNA passes (>20 mm) aimed in the direction of a visible or approximated central mass. Rapid on-site evaluation of specimens was used. RESULTS: Superficial FNA was diagnostic in 11 patients (35.5%), whereas deeper FNA was diagnostic in 23 patients (74.2%, p = 0.002). Deeper FNA confirmed malignancy in all cases with diagnostic superficial FNA. We observed no pneumothoraces or major hemorrhage. All patients were ultimately diagnosed with malignancy (bronchogenic carcinoma, n = 30; lymphoma, n = 1). CONCLUSIONS: US-assisted FNA of drowned lung has an acceptable diagnostic yield and is safe.

The diagnostic yield and safety of ultrasound-assisted transthoracic biopsy of mediastinal masses.

BACKGROUND: Ultrasound (US)-assisted transthoracic biopsy offers a less invasive alternative to surgical biopsy in the setting of mediastinal masses. OBJECTIVES: The aim of this 1-year prospective study was to assess the diagnostic yield and safety of a novel single-session sequential approach of US-assisted transthoracic fine-needle aspirations (TTFNA) with rapid on-site evaluation (ROSE) followed by cutting needle biopsies (CNB) performed by physicians on patients with anterosuperior mediastinal masses. METHODS: US-assisted TTFNA with ROSE was performed on 45 consecutive patients (49.5 ± 27.7 years, 24 males), immediately followed by CNB where a provisional diagnosis of epithelial carcinoma or tuberculosis could not be established, provided a safety range could be assured. RESULTS: TTFNA alone was deemed adequate by means of ROSE in 27 (60%) patients. CNB could be performed in 17 of the remaining 18. The on-site diagnosis corresponded to the final diagnosis in 26/45 (57.8%). An accurate cytological diagnosis was made in 33 (73.3%), and was more likely to be diagnostic in epithelial carcinoma and tuberculosis (28/30) than all other pathologies (5/15, p < 0.001). CNB yielded a diagnosis in 15/17 (88.2%). Overall, 42/45 patients were diagnosed by the single-session approach (93.3%). The final diagnoses included 41 neoplasms, with small cell lung cancer (n = 13) the commonest diagnosis. We observed no pneumothorax or major haemorrhage. CONCLUSIONS: A single-session sequential approach of US-assisted TTFNA with ROSE followed by CNB, where indicated, has a high diagnostic yield for anterosuperior mediastinal masses, is safe and offers an alternative to surgical biopsy.

[Smoking cessation training for physicians and other health professionals in Switzerland]. / Rauchstopp-Weiterbildung für Arzte und nicht-ärztliche Fachpersonen in der Schweiz.

Almost one third of the Swiss population smokes. Of these persons a large percentage would like to quit smoking each year. It is well known that the odds to quit successfully are improved by professional counseling and medication support. In order to counsel the numerous smokers interested in quitting a sufficient number of professionals needs to be trained in smoking cessation. For this training a short and extended course in smoking cessation for physicians is available (Frei von Tabak project). For non-physician health professionals there is a postgraduate course in tobacco prevention and smoking cessation and for both groups of professionals there is the Hospital QuitSupport workshop, which aims to support and promote hospital-based smoking cessation counseling. Smoking cessation counseling by physicians is remunerated in the outpatient setting. For non-physician smoking cessation counselling, however, there is no such tarif for remuneration. This drawback presents a considerable obstacle for the establishment of a large-scale smoking cessation counseling network in Switzerland.

Treatment of heterogeneous emphysema using the spiration IBV valves.

Ninety-eight emphysema patients were treated at 13 international sites during a 3-year series of single-arm, open-label studies with the IBV valve and a multi-lobar treatment approach. Fifty six percent of subjects had a clinically meaningful improvement in health-related quality of life, but standard pulmonary function and exercise studies were insensitive effectiveness measures. Quantitative CT analyses of regional lung changes showed lobar volume changes in over 85% of subjects. Lung volume reduction was an uncommon mechanism for a treatment response with bilateral upper lobe treatment. A redirection of inspired air, an interlobar shift to health-ier lung tissue, was the most common mechanism for a valve treatment response.

Safety of pleurodesis with talc poudrage in malignant pleural effusion: a prospective cohort study.

BACKGROUND: Talc is the most effective chemical pleurodesis agent for patients with malignant pleural effusion. However, concerns have arisen about the safety of intrapleural application of talc, after reports of development of acute respiratory distress syndrome in 1-9% of treated patients. Our aim was to establish whether use of large-particle-size talc is safe in patients with malignant pleural effusion. METHODS: We did a multicentre, open-label, prospective cohort study of 558 patients with malignant pleural effusion who underwent thoracoscopy and talc poudrage with 4 g of calibrated French large-particle talc in 13 European hospitals, and one in South Africa. The primary endpoint was the occurrence of acute respiratory distress syndrome after talc pleurodesis. FINDINGS: No patients developed acute respiratory distress syndrome (frequency 0%, one-sided 95% CI 0-0.54%). 11 (2%) patients died within 30 days. Additionally, seven patients had non-fatal post-thoracoscopy complications (1.2%), including one case of respiratory failure due to unexplained bilateral pneumothorax. INTERPRETATION: Use of large-particle talc for pleurodesis in malignant pleural effusion is safe, and not associated with the development of acute respiratory distress syndrome.

Promoting hospital-based smoking cessation services at major Swiss hospitals: a before and after study.

QUESTIONS UNDER STUDY: Whether a 1-year nationwide, government supported programme is effective in significantly increasing the number of smoking cessation clinics at major Swiss hospitals as well as providing basic training for the staff running them. METHODS: We conducted a baseline evaluation of hospital services for smoking cessation, hypertension, and obesity by web search and telephone contact followed by personal visits between October 2005 and January 2006 of 44 major public hospitals in the 26 cantons of Switzerland; we compared the number of active smoking cessation services and trained personnel between baseline to 1 year after starting the programme including a training workshop for doctors and nurses from all hospitals as well as two further follow-up visits. RESULTS: At base line 9 (21%) hospitals had active smoking cessation services, whereas 43 (98%) and 42 (96%) offered medical services for hypertension and obesity respectively. Hospital directors and heads of Internal Medicine of 43 hospitals were interested in offering some form of help to smokers provided they received outside support, primarily funding to get started or to continue. At two identical workshops, 100 health professionals (27 in Lausanne, 73 in Zurich) were trained for one day. After the programme, 22 (50%) hospitals had an active smoking cessation service staffed with at least 1 trained doctor and 1 nurse. CONCLUSION: A one-year, government-supported national intervention resulted in a substantial increase in the number of hospitals allocating trained staff and offering smoking cessation services to smokers. Compared to the offer for hypertension and obesity this offer is still insufficient.

Stair climbing in the functional assessment of lung resection candidates.

BACKGROUND: Algorithms for the pre-operative evaluation of lung resection candidates with impaired lung function invariably include maximum oxygen uptake (VO(2)MAX) as a critical parameter of functional reserves, with a VO(2)MAX >or=20 ml/kg/min generally considered sufficient for pneumonectomy. Stair climbing is a low-cost alternative to assess exercise capacity. OBJECTIVES: As stair climbing is not standardised, we aimed to compare the altitude reached and the speed of ascent with VO(2)MAX measured by cycle ergometry. METHODS: We prospectively enrolled 44 pulmonary resection candidates (mean age: 47.6 +/- 12.5 years) with an FEV(1) <80%. Patients were asked to climb as high and as fast as they could, to a maximum elevation of 20 m. The altitude reached and the average speed of ascent were compared to VO(2)MAX. RESULTS: Forty-three patients reached a 20-metre elevation. Thirteen of them, as well as the patient who did not reach this height, had a VO(2)MAX <20 ml/kg/min. There was a linear correlation between speed of ascent and VO(2)MAX/kg (R(2) = 0.67), but not between altitude and VO(2)MAX/kg. All 24 patients with a speed >or=15 m/min had a VO(2)MAX >or=20 ml/kg/min. Thirty-nine of 40 patients with a speed >or=12 m/min had a VO(2)MAX >or=15 ml/kg/min. CONCLUSIONS: The average speed of ascent during stair climbing was an accurate semiquantitative predictor of VO(2)MAX/kg, whereas altitude was not. We were able to identify potential cut-off values for lobectomy or pneumonectomy. Pending validation with clinical endpoints, stair climbing may replace formal exercise testing at much lower costs in a large proportion of lung resection candidates.

Parapneumonic pleural effusion and empyema.

At least 40% of all patients with pneumonia will have an associated pleural effusion, although a minority will require an intervention for a complicated parapneumonic effusion or empyema. All patients require medical management with antibiotics. Empyema and large or loculated effusions need to be formally drained, as well as parapneumonic effusions with a pH <7.20, glucose <3.4 mmol/l (60 mg/dl) or positive microbial stain and/or culture. Drainage is most frequently achieved with tube thoracostomy. The use of fibrinolytics remains controversial, although evidence suggests a role for the early use in complicated, loculated parapneumonic effusions and empyema, particularly in poor surgical candidates and in centres with inadequate surgical facilities. Early thoracoscopy is an alternative to thrombolytics, although its role is even less well defined than fibrinolytics. Local expertise and availability are likely to dictate the initial choice between tube thoracostomy (with or without fibrinolytics) and thoracoscopy. Open surgical intervention is sometimes required to control pleural sepsis or to restore chest mechanics. This review gives an overview of parapneumonic effusion and empyema, focusing on recent developments and controversies.

Evaluation of adapted whole-blood interferon-gamma release assays for the diagnosis of pleural tuberculosis.

BACKGROUND: Pleural tuberculosis (TB) remains difficult to diagnose despite numerous diagnostic tools. Recently, in vitro interferon (IFN)-gamma-based assays have been introduced in the diagnosis of latent TB, but these techniques have not been established in the diagnosis of active TB disease, including pleural TB. OBJECTIVES: It was the aim of this study to assess the accuracy of the commercially available QuantiFERON TB Gold assay and adapted variants of the assay, using pleural fluid or isolated pleural fluid cells for the diagnosis of pleural TB. METHODS: We recruited 66 consecutive patients with a pleural effusion of unknown cause presenting at a tertiary academic health care centre in Cape Town, South Africa, a high prevalence area of TB. Blood and pleural fluid were collected at presentation for IFN-gamma assays and the results evaluated for diagnostic accuracy. RESULTS: The clinical diagnosis was TB in 30 (46%), malignancy in 20 (30%), parapneumonic effusion/empyema in 8 (12%) and effusion due to other causes in 8 patients (12%). Ex vivo pleural fluid IFN-gamma levels accurately identified TB in all patients and were superior to the QuantiFERON In Tube assay using blood and pleural fluid (73 and 57% sensitivity, with 71 and 87% specificity, respectively) and the QuantiFERON Gold assay applied to isolated pleural fluid cells (100% sensitivity and 67% specificity). CONCLUSION: The ex vivo pleural fluid interferon-gamma level is an accurate marker for the diagnosis of pleural TB, and the QuantiFERON TB Gold assay performed with peripheral blood or adapted for pleural fluid cells does not add diagnostic value.

Assessing regional lung function.

The assessment of regional lung function to predict postoperative function is integral to preoperative evaluation of pulmonary resection candidates who have impaired lung function. The four validated ways are: anatomic calculation, split radionucleotide perfusion scanning with single photon emission CT (SPECT), quantitative CT scanning, and dynamic perfusion MRI. Estimations of predicted postoperative lung function based on anatomical calculations are the simplest, tend to overestimate postresectional functional loss, and should be performed in most operative candidates. Patients requiring further evaluation require one of the other techniques: SPECT, quantitative CT, or MRI. All effectively predict postoperative forced expiratory volume in 1 second (FEV1). Cost, local expertise and availability, and the need to predict postoperative VO maximum oxygen consumption (VO2 max) dictate the clinician's choice.

The role of diffusing capacity and exercise tests.

Beside pulmonary function tests, other measures of cardiopulmonary fitness have been shown to be useful for preoperative risk stratification. Reduced values of carbon monoxide lung diffusion capacity and its predicted postoperative value have been reported to be associated with postoperative complications and mortality. The most widely used low-technology exercise tests, which include 6 minutes of walking and stair climbing, have been reported to be valid predictors of complications. Patients with an impaired performance at these tests need to undergo a formal cardiopulmonary test with measurement of maximum oxygen consumption at cycle-ergometry or treadmill. Functional algorithms have been proposed that incorporate all these tests, with the aim to assist in defining the surgical risk.