Beta-blockers are under-prescribed in patients with chronic obstructive pulmonary disease and co-morbid cardiac disease.

The use of beta-blockers in patients with chronic obstructive pulmonary disease and co-morbid cardiovascular disease is controversial, despite increasing evidence to support their use as safe and efficacious. This study retrospectively assessed the rates of beta-blocker prescription in patients admitted to two Australian tertiary hospitals for acute exacerbation of chronic obstructive pulmonary disease. This revealed that less than half of patients (45%) with known cardiac indications were receiving beta-blocker therapy, evident across all degrees of airways disease severity. Further work is needed to ensure that medical management of this patient group is optimised.

CD11b immunophenotyping identifies inflammatory profiles in the mouse and human lungs.

The development of easily accessible tools for human immunophenotyping to classify patients into discrete disease endotypes is advancing personalized therapy. However, no systematic approach has been developed for the study of inflammatory lung diseases with often complex and highly heterogeneous disease etiologies. We have devised an internally standardized flow cytometry approach that can identify parallel inflammatory alveolar macrophage phenotypes in both the mouse and human lungs. In mice, lung innate immune cell alterations during endotoxin challenge, influenza virus infection, and in two genetic models of chronic obstructive lung disease could be segregated based on the presence or absence of CD11b alveolar macrophage upregulation and lung eosinophilia. Additionally, heightened alveolar macrophage CD11b expression was a novel feature of acute lung exacerbations in the SHIP-1(-/-) model of chronic obstructive lung disease, and anti-CD11b antibody administration selectively blocked inflammatory CD11b(pos) but not homeostatic CD11b(neg) alveolar macrophages in vivo. The identification of analogous profiles in respiratory disease patients highlights this approach as a translational avenue for lung disease endotyping and suggests that heterogeneous innate immune cell phenotypes are an underappreciated component of the human lung disease microenvironment.

Direct ultrasound localisation for pleural aspiration: translating evidence into action.

BACKGROUND: There is strong evidence that direct ultrasound localisation for pleural aspiration reduces complications, but this practice is not universal in Australia and New Zealand. AIMS: To describe the current utilisation and logistical barriers to the use of direct ultrasound localisation for pleural aspiration by respiratory physicians from Australia and New Zealand, and to determine the cost benefits of procuring equipment and training resources in chest ultrasound. METHODS: We surveyed all adult respiratory physician members of the Thoracic Society of Australia and New Zealand regarding their use of direct ultrasound localisation for pleural aspiration. We performed a cost-benefit analysis for acquiring bedside ultrasound equipment and estimated the capacity of available ultrasound training. RESULTS: One hundred and forty-six of 275 respiratory physicians responded (53% response). One-third (33.6%) of respondents do not undertake direct ultrasound localisation. Lack of training/expertise (44.6%) and lack of access to ultrasound equipment (41%) were the most frequently reported barriers to performing direct ultrasound localisation. An average delay of 2 or more days to obtain an ultrasound performed in radiology was reported in 42.7% of respondents. Decision-tree analysis demonstrated that clinician-performed direct ultrasound localisation for pleural aspiration is cost-beneficial, with recovery of initial capital expenditure within 6 months. Ultrasound training infrastructure is already available to up-skill all respiratory physicians within 2 years and is cost-neutral. CONCLUSION: Many respiratory physicians have not adopted direct ultrasound localisation for pleural aspiration because they lack equipment and expertise. However, purchase of ultrasound equipment is cost-beneficial, and there is already sufficient capacity to deliver accredited ultrasound training through existing services.

Clinical utility of sequential venous blood gas measurement in the assessment of ventilatory status during physiological stress.

BACKGROUND: Venous blood gases (VBG) are commonly utilised, particularly in the emergency setting, to assess and monitor patients at risk of ventilatory failure with limited evidence regarding their clinical utility in the assessment of ventilatory status over time. AIMS: This study aims to assess agreement between arterial and venous pH and partial pressure of carbon dioxide (pCO2) both before and after physiological stress, at each time point, and within the same subject between paired samples before and after bronchoscopy. METHODS: Prospective study of 30 patients undergoing flexible bronchoscopy under conscious sedation. Paired arterial and venous samples taken before and after bronchoscopy were analysed utilising descriptive statistics and bias plot (Bland-Altman) analysis to assess limits of agreement. RESULTS: Compared with baseline, post-bronchoscopy arterial blood gas and VBG showed reduced pH (-0.05 ± 0.05 and -0.04 ± 0.04 respectively) and increased arterial and venous pCO2 (5.9 ± 6.7 and 3.5 ± 5.5 mmHg respectively), the differences being statistically significant (P = 0.035). There was statistical agreement between arterial blood gas and VBG parameters; however, the limits of agreement were wide at rest and, for pCO2, widened further post-bronchoscopy. CONCLUSION: Sequential VBG provide an unpredictable means for assessing pCO2 in patients undergoing flexible bronchoscopy. Previously noted poor agreement between arterial and venous pCO2 worsens following physiological stress, with sequential VBG likely to underestimate changes in ventilatory status in patients with acute respiratory compromise, suggesting limited utility as a means for monitoring changes in ventilation.

Mediastinal staging of non-small-cell lung cancer among Australasian thoracic physicians: clinical practice and constraints on minimally invasive techniques.

BACKGROUND/AIM: We determined current practice among Australasian thoracic physicians in the mediastinal staging of non-small-cell lung cancer (NSCLC). We focused on the availability of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) and constraints to its use, as there has been no systematic analysis regarding the availability and uptake of this new technology among thoracic physicians. METHODS: Physician members of the Thoracic Society of Australia and New Zealand were emailed a survey seeking their current approach to three scenarios requiring mediastinal staging of NSCLC. Respondents were also asked for their preferred investigation for each scenario if any current constraints were removed. Relevant demographic information was sought. RESULTS: We received 164 responses from 512 Australasian physicians (34%). Without constraints, EBUS-TBNA was the preferred investigation for all three clinical scenarios, but only 33% of respondents had access to EBUS-TBNA. Constraints included lack of availability and lack of expertise. Reduced EBUS-TBNA access was associated with a number of clinician factors. CONCLUSIONS: Australasian thoracic physicians prefer EBUS-TBNA for the mediastinal staging of NSCLC, but access to EBUS-TBNA services is limited. We recommend targeted measures to improve access to EBUS-TBNA use and optimise mediastinal staging of NSCLC.

Changes in the BODE index, exacerbation duration and hospitalisation in a cohort of COPD patients.

INTRODUCTION: We investigated the relationship between frequency of exacerbation and duration and change in functional status, as measured by the BODE index in chronic obstructive pulmonary disease (COPD) patients. METHODS: This was a longitudinal cohort study of 56 patients with moderate to severe COPD. Body mass index, spirometry, Modified Medical Research Council (MMRC) dyspnoea score and six-minute walk distance (6MWD) were measured annually when the patients were clinically stable. Data on frequency and duration of COPD exacerbations occurring in the community and requiring hospitalisation were collected prospectively. Early stage exacerbations were identified through the use of individualised patient action plans and further reinforced by fortnightly phone contact. RESULTS: At the two-year follow-up, the BODE index increased in 33 patients, remained stable in 18 and decreased in five patients. Patients with increased BODE index had significantly higher hospital presentation rates and longer total bed-days compared to those with stable BODE index. Among the 33 patients with increased BODE index, 20 had lower 6MWD and higher MMRC scores, indicating deteriorating functional status, and 13 had higher levels of airway obstruction. Between these two subgroups, patients with deteriorating functional status had higher exacerbation frequency, longer exacerbation duration and higher inpatient bed-days. Linear regression showed that total annual duration of exacerbation was predictive of change in 6MWD. CONCLUSION: Change in the BODE index is a sensitive measure of deteriorating functional status in COPD patients. Duration of exacerbation has greater impact on functional status than frequency of exacerbation episodes.

Radial probe endobronchial ultrasound for the diagnosis of peripheral lung cancer: systematic review and meta-analysis.

Improved diagnostic sensitivity of bronchsocopy for the investigation of peripheral pulmonary lesions (PPLs) with the use of radial probe endobroncial ultrasound (EBUS) has been reported, although diagnostic performance varies considerably. A systematic review of published literature evaluating radial probe EBUS accuracy was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. Sub-group analysis and linear regression was used to identify possible sources of study heterogeneity. 16 studies with 1,420 patients fulfilled inclusion criteria. Significant inter-study variation in EBUS method was noted. EBUS had point specificity of 1.00 (95% CI 0.99-1.00) and point sensitivity of 0.73 (95% CI 0.70-0.76) for the detection of lung cancer, with a positive likelihood ratio of 26.84 (12.60-57.20) and a negative likelihood ratio of 0.28 (0.23-0.36). Significant inter-study heterogeneity for sensitivity was observed, with prevalence of malignancy, lesion size and reference standard used being possible sources. EBUS is a safe and relatively accurate tool in the investigation of PPLs. Diagnostic sensitivity of EBUS may be influenced by the prevalence of malignancy in the patient cohort being examined and lesion size. Further methodologically rigorous studies on well-defined patient populations are required to evaluate the generalisability of our results.

Bronchoscopic evaluation of the mediastinum using endobronchial ultrasound: a description of the first 216 cases carried out at an Australian tertiary hospital.

BACKGROUND: Performance of linear probe endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for staging non-small-cell lung cancer has been extensively studied. Alternate indications for its use are less well characterised, and performance in other clinical settings may differ. METHODS: We examined a prospectively collected cohort comprising the first 215 patients undergoing EBUS-TBNA at our institution. Patients were analysed according to the clinical and radiological indication for referral. We also examined the effect of the procedural learning curve on diagnostic sensitivity. RESULTS: A total of 215 patients underwent 216 EBUS-TBNA procedures. EBUS-TBNA returned adequate tissue for cytopathological analysis in 202 of 216 procedures (94%). Overall sensitivity for detection of malignancy was 0.92 (95% confidence interval 0.86-0.96); however, this varied according to the primary indication for EBUS-TBNA. Diagnostic sensitivity was high among all sub-groups, but the negative predictive value varied depending on the clinical indication for the procedure. We estimate 104 invasive surgical procedures and 32 inpatient admissions were avoided by use of EBUS-TBNA. Significant improvement in diagnostic performance was seen after 20 procedures were completed, and diagnostic accuracy did not peak until after 50 procedures. CONCLUSIONS: EBUS-TBNA is able to confirm accurately histologically a large number of disease processes, both malignant and benign, in all clinical indications studied. The procedure is safe even when carried out by proceduralists with minimal prior experience. Diagnostic performance continues to improve beyond 50 cases carried out.

Cavitating lymph node metastasis demonstrated by endobronchial ultrasound.

Cavitation of primary non-small cell lung carcinoma (NSCLC) occurs in a small number of patients. We report a case of cavitation of lymph node metastases in NSCLC. CT chest showed central low attenuation of the subcarinal lymph node, suggestive of necrosis, and endobronchial ultrasound (EBUS) imaging demonstrated two cystic spaces within the lymph node. Transbronchial needle aspiration of the cystic space confirmed the presence of metastatic NSCLC. Cystic necrosis was only demonstrable by EBUS. The incidence of such findings is unknown, however with the increasing use of EBUS for evaluation of the mediastinum such images may be more commonly encountered in the future.

Endobronchial ultrasound staging of thyroid lesion in small cell lung carcinoma.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has proven its utility in the mediastinal staging of lung cancer. Its use in the evaluation of thyroid lesions has not previously been described. We report the safe and effective use of EBUS-TBNA to evaluate a thyroid lesion in a patient with suspected lung cancer at the time of diagnostic bronchoscopy. Use of this method in the evaluation of thyroid lesions may be considered in patients with coexistent mediastinal or hilar lesions, or for lesions not accessible to a percutaneous approach.

Incidence of bacteraemia following endobronchial ultrasound-guided transbronchial needle aspiration.

Few data exist concerning possible infectious complications associated with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The present prospective evaluation was undertaken in order to determine the incidence of bacteraemia and infectious complications associated with EBUS-TBNA. Consecutive patients undergoing EBUS-TBNA for evaluation of mediastinal or hilar lymph node lesions were studied. Venesection was performed within 60 s of TBNA for aerobic and anaerobic blood culture. Sterile saline washing of TBNA needles was also performed. Patients with positive blood cultures were reviewed immediately, and all patients underwent clinical review within 1 week of EBUS-TBNA. A total of 43 patients underwent EBUS-TBNA, with bacteraemia demonstrated in three (7%). All bacterial isolates were typical oropharyngeal commensal organisms. The TBNA needle washing culture was positive in 15 (35%) patients. None of the three bacteraemic patients had clinical features suggestive of infection, and no complications were seen among the cohort. The incidence of bacteraemia following EBUS-TBNA is comparable to that following routine flexible bronchoscopy. Performance of TBNA does not appear to measurably increase the risk of bacteraemia over that associated with insertion of the bronchoscope into the airway. Contamination of the TBNA needle with oropharyngeal commensal bacteria is common; however, clinically significant infection following EBUS-TBNA appears rare.

Advances in lung cancer diagnosis and staging: endobronchial ultrasound.

BACKGROUND: Endobronchial ultrasound (EBUS) is an accurate and relatively less invasive procedure for the diagnosis of lung lesions and mediastinal lymph node staging for lung cancer. We aimed to evaluate the clinical utility and safety of this new EBUS service established in our hospital. METHODS: Consecutive patients who underwent EBUS-transbronchial lung biopsy (EBUS-TBLB) for biopsy of peripheral pulmonary lesions or for transbronchial needle aspiration (TBNA) of mediastinal lymph node enlargement were included in this audit. Demographic and clinical data were obtained prospectively. Diagnostic yield from the results of EBUS was compared to other clinical information obtained. RESULTS: Thirty-eight patients underwent EBUS over a 10-month period. The yield from EBUS-TBLB was 62%. The average size of the lung lesions biopsied was 3.5 cm and 62% were located in the upper lobes. Malignancy was diagnosed in 14 cases and a benign aetiology in four. The yield from EBUS-TBNA was 88% and the average size of the lymph nodes was 2.3 cm. The lymph nodes were all located in the subcarinal station except for two that were in the lower paratracheal station. Malignancy was diagnosed in 10 cases on TBNA and 4 cases had benign pathology. There was one complication seen (small pneumothorax). CONCLUSION: EBUS is safe and an effective method for both, diagnosis of peripheral pulmonary lesions and staging for lung cancer.

The natural history of asthma from childhood to adulthood.

Medical Practitioners are often questioned regarding the prognosis of a child with asthma. We have performed a literature review of the natural history of childhood asthmatics. Factors which affect the natural history and prognosis of childhood asthma are discussed. Current evidence suggests that evolution of asthma severity is fairly predictable. Features of childhood asthma such as severity, duration, atopy, bronchial hyperresponsiveness and exposure to smoking can predict the course of asthma into adulthood. Most children with mild intermittent asthma will outgrow their asthma, or have mild episodic asthma. Early commencement of anti-inflammatory therapy, such as inhaled corticosteroids may prevent the progression of the disease. Most patients with mild asthma have good functional outcome and low healthcare utilisation.

Long-acting beta2-agonists versus theophylline for maintenance treatment of asthma.

BACKGROUND: Theophylline and long acting beta-2 agonists are bronchodilators used for the management of persistent asthma symptoms, especially nocturnal asthma. They represent different classes of drug with differing side-effect profiles. OBJECTIVES: To assess the comparative efficacy, safety and side-effects of long-acting beta-2 agonists and theophylline in the maintenance treatment of adults and adolescents with asthma. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register and reference lists of articles. We also contacted authors of identified RCTs for other relevant published and unpublished studies and pharmaceutical manufacturers. Most recent search: November 2006. SELECTION CRITERIA: All included studies were RCTs involving adults and children with clinical evidence of asthma. These studies must have compared oral sustained release and/or dose adjusted theophylline with an inhaled long-acting beta-2 agonist. DATA COLLECTION AND ANALYSIS: In original review, two reviewers independently assessed trial quality and extracted data, similarly in this update two reviewers undertook this. Study authors were contacted for additional information. MAIN RESULTS: Thirteen studies with a total of 1344 participants met the inclusion criteria of the review. They were of varying quality. There was no significant difference between salmeterol and theophylline in FEV(1) predicted (6.5%; 95% CI -0.84 to 13.83). However, salmeterol treatment led to significantly better morning PEF (mean difference 16.71 L/min, 95% CI 8.91 to 24.51) and evening PEF (mean difference 15.58 L/min, 95% CI 8.33 to 22.83). Salmeterol also reduced the use of rescue medication. Formoterol, used in two studies was reported to be as effective as theophylline. Bitolterol, used in only one study, was reported to be less effective than theophylline. Participants taking salmeterol experienced fewer adverse events than those using theophylline (Parallel studies: Relative Risk 0.44; 95% CI 0.30 to 0.63, Risk Difference -0.11; 95% CI -0.16 to -0.07, Numbers Needed to Treat (NNT) 9; 95% CI 6 to 14). Significant reductions were reported for central nervous system adverse events (Relative Risk 0.50; 95% CI 0.29 to 0.86, Risk Difference -0.07; 95% CI -0.12 to -0.02, NNT 14; 95% CI 8 to 50) and gastrointestinal adverse events (Relative Risk 0.30; 95% CI 0.17 to 0.55, Risk Difference -0.11; 95% CI -0.16 to -0.06, NNT 9; 95% CI 6 to 16). AUTHORS' CONCLUSIONS: Long-acting beta-2 agonists, particularly salmeterol, are more effective than theophylline in improving morning and evening PEF, but are not significantly different in their effect on FEV1. There is evidence of decreased daytime and nighttime short-acting beta-2 agonist requirement with salmeterol. Fewer adverse events occurred in participants using long-acting beta-2 agonists (salmeterol and formoterol) as compared to theophylline.

Inhaled corticosteroids compared to placebo for prevention of exercise induced bronchoconstriction.

BACKGROUND: The pathogenesis of exercise induced bronchoconstriction is likely multifactorial and is not completely understood. Inflammation plays an important role in the pathogenesis of exercise induced bronchoconstriction in asthmatic subjects but the evidence seems less strong in non-asthmatic subjects. The management of exercise induced bronchoconstriction focuses on prevention, through both pharmacologic and non-pharmacologic interventions. OBJECTIVES: The objectives of this review were to evaluate the use of inhaled corticosteroids in the treatment of exercise induced bronchoconstriction in a systematic way. Specifically, the review was designed to: determine whether inhaled corticosteroids (compared to placebo) has an attenuating effect on exercise induced bronchoconstriction in adult and pediatric asthmatic patients; estimate the magnitude of the attenuating effect. SEARCH STRATEGY: We searched the Cochrane Airways Review Group Specialised Register of trials, the Cochrane Central Register of Controlled Trials, review articles, textbooks and reference list of articles. SELECTION CRITERIA: Randomised trials in adults or children comparing inhaled corticosteroids with placebo to prevent bronchoconstriction in patients with exercise induced bronchoconstriction. DATA COLLECTION AND ANALYSIS: Trial quality assessment and data extraction were conducted independently by two reviewers. MAIN RESULTS: The results from six randomised controlled trials involving 123 participants were analyzed (two trials involving adults and four involving children). Combining results from the two parallel studies with at least 4 weeks duration of inhaled corticosteroids, the use of inhaled corticosteroids significantly attenuated the percent fall index in forced expiratory volume in 1 second (WMD = 14.07%; 95% CI: 11.62% to 16.52%). The result from one crossover study with duration of inhaled corticosteroids of 4 weeks revealed significant attenuation of percent fall in forced expiratory volume in 1 second ( WMD = 6.90%; 95% CI: 1.40% to 12.40%) and the percent fall in peak expiratory flow ( WMD =11.50%; 95% CI: 6.31% to 16.69%). The small amount of data from placebo-controlled trials using a single treatment do not currently allow conclusions to be drawn. AUTHORS' CONCLUSIONS: Inhaled corticosteroids used for 4 weeks or more before exercise testing significantly attenuated exercise-induced bronchoconstriction. The relative benefits of inhaled corticosteroids compared to other forms of exercise induced bronchoconstriction treatment (sodium cromoglycate, nedocromil sodium, salbutamol, and other anti-inflammatory agents) remains unclear.

Evidence-based pharmacologic treatment for mild asthma.

BACKGROUND: Although mild asthmatics form the majority of asthma sufferers, there is a relative paucity of evidence-based treatment compared with severe asthmatics. OBJECTIVE: We have performed an up-to-date review of the literature on therapy in this group of patients who form an overlooked but important majority. Potential trials were identified through MEDLINE (1965-2007) and Cochrane library (up to February 2007). DISCUSSION: Recent trials have shown that inhaled corticosteroids (ICS) remain the cornerstone of treatment for patients with mild persistent asthma. Early intervention with ICS decreases the risk of severe exacerbations and improves asthma control in patients with mild persistent asthma of recent onset. ICS are superior to leukotriene receptor antagonists and xanthines for control of asthma and in the improvement of lung functions. The addition of long-acting beta2-agonist may be considered in those with moderately persistent asthma or whom asthma is not well controlled with low doses of ICS.