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).

Serodiagnostic markers for the prediction of the outcome of intensive phase tuberculosis therapy.

Treatment failure and relapse may affect many tuberculosis (TB) patients who undergo standard anti-TB therapy. Several independent studies suggested unsuccessful sputum culture conversion at month 2 of treatment (slow response) as risk factor for treatment failure and relapse. However, earlier than month 2 identification of patients with a high risk for poor treatment outcome would offer significant clinical trial and individual patient care benefits. The sensitivity and specificity of serological IgG and IgA responses against four recombinant mycobacterial antigens (ABC transporter PstS3, secreted l-alanine dehydrogenase, culture filtrate protein Tpx and 6 kDa early secretory antigenic target esxa (ESAT-6)) were evaluated separately in a blinded fashion in 21 smear-positive pulmonary TB patient sera taken at diagnosis before commencement of directly observed anti-TB treatment short course comprising 13 slow responder and eight fast responder subjects. We observed a general pattern of higher antibody levels in sera of slow responders. Most pronounced were high levels of anti-alanine dehydrogenase IgG, anti-Tpx IgG, anti-ESAT-6 IgG and anti-ESAT-6 IgA antibodies at diagnosis being associated with slow response with 100% specificity each and 46.2, 53.8, 53.8 or 53.8% sensitivity, respectively, when compared to fast response (P = 0.020, 0.021, 0.040 and 0.011, respectively). Discriminant analysis showed that the combined use of anti-Tpx IgG and anti-ESAT-6 IgA antibody titers before treatment predicted slow responders with 90.5% accuracy. These preliminary results suggest that combinations of serodiagnostic markers measured prior to initiation of treatment may be suitable for the prediction of early treatment response. This approach holds promise and requires further evaluation for its utility in the prediction of treatment failure and relapse, the evaluation of new TB therapeutics, as well as in the care of individual patients.

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.

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.

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.

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.

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.

Comparison of the quality of smears in transbronchial fine-needle aspirates using two staining methods for rapid on-site evaluation.

Transbronchial needle aspiration (TBNA) via flexible bronchoscopy is a well-established sampling modality for lung masses. The procedure is useful in the diagnosis of neoplastic and non-neoplastic lesions as well as for staging of bronchogenic carcinoma. Rapid on-site evaluation (ROSE) adds value as it has the advantage of triaging material during the procedure so avoiding a battery of investigations. Frequently used rapid stains are the modified Wright-Giemsa water-based stain (WG-ROSE) and the alcohol-based modified Papanicolaou stain (Pap-ROSE). Final review of laboratory-based Giemsa and Pap stains supplemented by ancillary investigations is essential for quality assurance. To investigate whether and how ROSE influenced the quantity and quality of the material submitted to the laboratory we randomized 126 patients to WG-ROSE, requiring only one pathologist on-site, or combined WG- and Pap-ROSE, requiring an additional person on-site to assist with staining. In those patients with positive TBNA we graded the laboratory-based slides of the first pass containing diagnostic material into insufficient, suspicious, adequate and excellent. The first diagnostic pass was found after 3.06 ± 1.94 (SD) passes and 3.13 ± 2.16 passes with WG-ROSE and combined ROSE (P = 0.87), respectively. Following WG-ROSE and combined ROSE 69% and 71.1% (P = 0.509) of slides were diagnostic (adequate or excellent) on laboratory-based Giemsa stains, and 93.3% and 100% (P = 0.134) were scored adequate or excellent on laboratory-based Pap stains. We concluded that the less costly and labour intensive WG-ROSE procedure is adequate for TBNA. This has cost implications especially in resource poor settings.

Functional evaluation before lung resection.

Lung cancer is the leading cause of cancer-related death worldwide, and lung resection remains the only curative approach. In the Western world, lung cancer is one of the main indications for lung resection, despite only 15% to 25% of all lung cancers being operable at the time of presentation. In most cases of operable lung cancer, a substantial part of functional lung tissue has to be resected, leading to a permanent loss of pulmonary function. Resection in patients with insufficient pulmonary reserves can result in permanent respiratory disability. This article reviews the current standards of preoperative assessment.

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.

Effects of varenicline in adult smokers: a multinational, 24-week, randomized, double-blind, placebo-controlled study.

BACKGROUND: Prevalence rates of smoking are rising in developing countries. Previous trials evaluating the efficacy and tolerability of the smoking-cessation medication varenicline have used largely participants of Caucasian origin. OBJECTIVE: This study was conducted to evaluate the efficacy and tolerability of varenicline in populations of participants from Latin America, Africa, and the Middle East to investigate potential differences in the therapeutic response to varenicline. METHODS: This multinational, randomized, double-blind, placebo-controlled trial was conducted at 42 centers in 11 countries (Latin America: Brazil, Colombia, Costa Rica, Mexico, and Venezuela; Africa: Egypt and South Africa; Middle East: Jordan, Lebanon, Saudi Arabia, and the United Arab Emirates). Participants were male and female smokers aged 18 to 75 years who were motivated to stop smoking; smoked ≥10 cigarettes/d, with no cumulative period of abstinence >3 months in the previous year; and who had no serious or unstable disease within the previous 6 months. Subjects were randomized in a 2:1 ratio to receive varenicline 1 mg or placebo, BID for 12 weeks, with a 12-week nontreatment follow-up. Brief smoking-cessation counseling was provided. The main outcome measures were carbon monoxide-confirmed continuous abstinence rate (CAR) at weeks 9 to 12 and weeks 9 to 24. Adverse events (AEs) were recorded for tolerability assessment. RESULTS: Overall, 588 subjects (varenicline, 390; placebo, 198) were randomized and treated. The mean (SD) ages of subjects in the varenicline and placebo groups were 43.1 (10.8) and 43.9 (10.8) years, respectively; 57.7% and 65.7% were male; and the mean (SD) weights were 75.0 (16.0) and 76.7 (16.3) kg (range, 40.0-130.0 and 45.6-126.0 kg). CAR at weeks 9 to 12 was significantly higher with varenicline than with placebo (53.59% vs 18.69%; odds ratio [OR] = 5.76; 95% CI, 3.74-8.88; P < 0.0001), and this rate was maintained during weeks 9 to 24 (39.74% vs 13.13%; OR = 4.78; 95% CI, 2.97-7.68; P < 0.0001). Nausea, headache, and insomnia were the most commonly reported AEs with varenicline and were reported numerically more frequently in the varenicline group compared with the placebo group. Serious AEs (SAEs) were reported in 2.8% of varenicline recipients compared with 1.0% in the placebo group, with 6 subjects reporting psychiatric SAEs compared with none in the placebo group. CONCLUSION: Based on these data, varenicline was apparently efficacious and generally well tolerated as a smoking-cessation aid in smokers from selected sites in Latin America, Africa, and the Middle East. ClinicalTrials.gov identifier: NCT00594204.

Radiologic features, staging, and operability of primary lung cancer in the Western cape, South Africa: a 1-year retrospective study.

INTRODUCTION: This retrospective study was performed to evaluate the radiologic features, staging, and resectability of lung cancer at the time of presentation in patients from the Western Cape of South Africa. METHOD: We included all patients with primary lung cancer reviewed during a 12-month period (January 2009 to December 2009) who had a definite tissue diagnosis and whose staging computed tomography scans were available. Fifteen radiologic parameters were assessed. RESULTS: Data were complete in 204 patients. The proportion and median size of the various histologic subtypes were as follows: adenocarcinoma 53.9%, 53.4 mm; squamous cell 25.9%, 80.2 mm; small cell 14.2%, 80.8 mm; large cell 2.4%, 74.2 mm; bronchioloalveolar carcinoma 1.5%, 50.0 mm; and others 2%, 57.6 mm, respectively. The overall median size of tumor was 61.5 mm. Tumors were located centrally in 43.6%, peripherally in 46.6%, indeterminate in 9.8%, mediastinal in 11.3%, right lung in 53.4%, and in the left lung in 35.3%. Tuberculosis-related lung fibrosis was present in 16%, but only 5.4% patients had coexisting tumor and fibrosis at the same site. We observed no difference in the proportion of coexisting fibrosis between adenocarcinoma and squamous carcinoma. Only 16.2% of the patients were potential candidates for radical treatment, with an actual resection rate of 4.4%. CONCLUSIONS: In the Western Cape, adenocarcinoma is the commonest histologic subtype of bronchogenic carcinoma. Most patients present with late-stage primary tumors, and the percentage of patients with potentially resectable cancer is much lower than in Europe.

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.