Pleura revisited: From histology and pathophysiology to pathology and molecular biology.

Pleural cavity has an interesting physiology that when impaired gives rise to pleural effusions a rather frequent problem in respiratory medicine practice. Their aetiology varies widely producing distinct pathological lesions with different prognosis and treatment. The basic morphological features of pleural diseases, neoplastic and non-neoplastic, will be analysed in this review with an emphasis to their pathophysiology, differential diagnosis and clinicopathological correlations.

The Electronic Nose's Emerging Role in Respiratory Medicine.

New interest has grown in the respiratory disorder diagnosis and monitoring, throughout electronic nose technologies. This technology has several advantages compared to classic approach. In this short letter, we aim to emphasize electronic nose role in respiratory medicine.

Instantaneous frequency based index to characterize respiratory crackles.

BACKGROUND: Crackle is a lung sound widely employed by health staff to identify respiratory diseases. The two-cycle duration (2CD) is a quantitative index pointed out by the American Thoracic Society and the European Respiratory Society to classify respiratory crackles as fine or coarse. However, this index, measured in the time domain, is highly affected by noise and filters of recording systems. Such factors hamper the analysis of data reported by different research groups. This work proposes a new index based on the instantaneous frequency of crackles estimated by means of discrete-time pseudo Wigner-Ville distribution. METHOD: Comparisons between 2CD and the proposed index were carried out for simulated and actual crackles. Normal breathing sounds were added to simulated crackles; the resulting signals were then applied to a band-pass filter that mimics those belonging to lung sound acquisition systems. Thus, the impact of noise and filtering on these two indices was assessed for simulated crackles. Kruskal-Wallis and Dunn's tests as well as Gaussian mixture model (GMM) were applied to the two indices measured from 382 actual crackles belonging to open databases. RESULTS: The proposed index is much less susceptible to waveform distortions due to noise and filtering when compared to the 2CD. Thus, the statistical analyses allow the identification of two classes of crackles from actual databases; the same does not occur when using 2CD. CONCLUSIONS: The new proposed index has the potential to contribute for a better characterization of crackles generated by different respiratory diseases, assisting their diagnosis during clinical exams.

Review of Recent Important Papers in Interventional Pulmonology.

Interventional pulmonology is an innovative branch of pulmonary medicine that uses minimally invasive diagnostic and therapeutic approaches to airway, parenchymal, and pleural disease. The author reviews recent high-impact trials including randomized trials describing the use of endobronchial coils and valves in the management of severe emphysema. Novel approaches to the palliation of malignant and benign pleural effusion including increasing the frequency of drainage and instillation of talc via tunneled pleural catheters are also presented. In addition, a recent consensus paper discussing the optimal use and technique of cryobiopsy in diffuse parenchymal disease is reviewed, as well as a systematic review and meta-analysis of its diagnostic yield. The final trial reviewed in this article describes the preliminary safety and efficacy study of a novel endobronchial, balloon, and injection catheter for the local administration of chemotherapy into the airway mucosa so as to minimize the systemic absorption of these agents.

Current Practice of Airway Stenting in the Adult Population in Europe: A Survey of the European Association of Bronchology and Interventional Pulmonology (EABIP).

BACKGROUND: Airway stenting (AS) commenced in Europe circa 1987 with the first placement of a dedicated silicone airway stent. Subsequently, over the last 3 decades, AS was spread throughout Europe, using different insertion techniques and different types of stents. OBJECTIVES: This study is an international survey conducted by the European Association of Bronchology and Interventional Pulmonology (EABIP) focusing on AS practice within 26 European countries. METHODS: A questionnaire was sent to all EABIP National Delegates in February 2015. National delegates were responsible for obtaining precise and objective data regarding the current AS practice in their country. The deadline for data collection was February 2016. RESULTS: France, Germany, and the UK are the 3 leading countries in terms of number of centres performing AS. These 3 nations represent the highest ranked nations within Europe in terms of gross national income. Overall, pulmonologists perform AS exclusively in 5 countries and predominately in 12. AS is performed almost exclusively in public hospitals. AS performed under general anaesthesia is the rule for the majority of institutions, and local anaesthesia is an alternative in 9 countries. Rigid bronchoscopy techniques are predominant in 20 countries. Amongst commercially available stents, both Dumon and Ultraflex are by far the most commonly deployed. Finally, 11 countries reported that AS is an economically viable activity, while 10 claimed that it is not. CONCLUSION: This EABIP survey demonstrates that there is significant heterogeneity in AS practice within Europe. Therapeutic bronchoscopy training and economic issues/reimbursement for procedures are likely to be the primary reasons explaining these findings.

Application of Mixed Effects Limits of Agreement in the Presence of Multiple Sources of Variability: Exemplar from the Comparison of Several Devices to Measure Respiratory Rate in COPD Patients.

INTRODUCTION: The Bland-Altman limits of agreement method is widely used to assess how well the measurements produced by two raters, devices or systems agree with each other. However, mixed effects versions of the method which take into account multiple sources of variability are less well described in the literature. We address the practical challenges of applying mixed effects limits of agreement to the comparison of several devices to measure respiratory rate in patients with chronic obstructive pulmonary disease (COPD). METHODS: Respiratory rate was measured in 21 people with a range of severity of COPD. Participants were asked to perform eleven different activities representative of daily life during a laboratory-based standardised protocol of 57 minutes. A mixed effects limits of agreement method was used to assess the agreement of five commercially available monitors (Camera, Photoplethysmography (PPG), Impedance, Accelerometer, and Chest-band) with the current gold standard device for measuring respiratory rate. RESULTS: Results produced using mixed effects limits of agreement were compared to results from a fixed effects method based on analysis of variance (ANOVA) and were found to be similar. The Accelerometer and Chest-band devices produced the narrowest limits of agreement (-8.63 to 4.27 and -9.99 to 6.80 respectively) with mean bias -2.18 and -1.60 breaths per minute. These devices also had the lowest within-participant and overall standard deviations (3.23 and 3.29 for Accelerometer and 4.17 and 4.28 for Chest-band respectively). CONCLUSIONS: The mixed effects limits of agreement analysis enabled us to answer the question of which devices showed the strongest agreement with the gold standard device with respect to measuring respiratory rates. In particular, the estimated within-participant and overall standard deviations of the differences, which are easily obtainable from the mixed effects model results, gave a clear indication that the Accelerometer and Chest-band devices performed best.

Parasternal intercostal electromyography: a novel tool to assess respiratory load in children.

BACKGROUND: Parasternal intercostal muscle electromyography (EMGpara) represents a novel tool to assess respiratory load when volitional techniques are not possible. This study examined the application of EMGpara in healthy, wheezy, and critically ill children. METHODS: Surface EMGpara was measured during tidal breathing in 92 healthy children, 20 wheezy preschool children (with measurements repeated following bronchodilator), and 25 mechanically ventilated children during supported ventilation and on continuous positive airways pressure. RESULTS: EMGpara was related to age, height, and weight in the healthy group (r = -0.623, -0.625, -0.641 respectively, all P < 0.0001). An age-based equation for predicted EMGpara was developed and patient data expressed as z-scores. EMGpara was higher in wheezy children prebronchodilator than healthy controls (median interquartile range (IQR) z-score 0.53 (0.07-1.94), P = 0.0073), falling to levels not different to healthy children postbronchodilator (-0.08 (-0.50-1.00)). In the critically ill children, EMGpara was higher (P < 0.0001) than in healthy subjects during both mechanical ventilation (median (IQR) z-score 1.14 (0.33-1.93)) and continuous positive airways pressure (1.88 (0.91-3.03)). CONCLUSION: EMGpara is feasible in children and infants both healthy and diseased, is raised in those with elevated respiratory load, and is responsive to clinical interventions. EMGpara represents a potential method to assess respiratory status in patients conventionally challenging to assess.

Ultrasound-guided Percutaneous Needle Aspiration by Pulmonologists: A Study of Factors With Impact on Procedural Yield and Complications.

BACKGROUND: The availability of portable ultrasound (US) guidance has led to usage by subspecialists outside of radiology. Several subspecialties now perform percutaneous fine-needle aspiration (PFNA) for lesions relevant to their expertise. This is a study of US-guided PFNA performed by interventional pulmonologists at a single institution. METHODS: We retrospectively reviewed serial US-guided PFNAs performed at an institution with the goals of defining yield, factors relating to yield, and complication rates. RESULTS: A total of 111 consecutive lesions were evaluated and 109 biopsied during the study period. Diagnosis was established in 81% of cases (90/109), with a total complication rate of 15% but only 1 case of a need for a higher level of care. Factors associated with increased diagnostic yield were suspicion of malignancy, increased size, and pleural adhesions (lack of pleural sliding). The presence of pleural sliding was associated with increased pneumothorax and decreased yield. CONCLUSIONS: US-guided PFNA is a valuable tool for the interventional pulmonologist. Both size and pleural sliding have an impact on diagnostic yield.

Field Safety Notes in Product Problems of Medical Devices for Use in Pulmonology.

The current European system for medical devices is governed by three EC directives: the Medical Device Directive 93/42/EEC, the In-Vitro Diagnostic Directive 98/79/EC and the Active Implantable Medical Device Directive 90/385/EEC and regulates marketing and post-market surveillance of medical devices in the European Economic Area. In cases of incidents and field safety corrective actions (FSCA) manufacturers have to inform the responsible Competent Authority, which is the Federal Institute for Drugs and Medical Devices (BfArM) and the public by field safety notices (FSN). In this study we analyzed FSN of medical devices exclusively serving for diagnostics or treatment in pulmonology (e.g. nebulizers, oxygen concentrators, pulse oximeters, lung function analyzers, and non-active devices for treatment). FSCA and FSN publicized by BfArM in 2005-2013 were analyzed in respect to the MEDDEV 2.12-1 rev 8. In total 41 FSCA were publicized for the included products. German and English FSN were found in 36/35 cases, respectively. FSN were clearly characterized as FSN in 22/20 cases and declaration of the type of action was found in 27/26 cases, respectively. Product names were provided in all cases. Lot numbers or other information for product characterization were available in 7/8 and 26/24 cases, respectively. Detailed information regarding FSCA and product malfunction were found in 27/33 and 36/35 cases, respectively. Information on product related risks with previous use of the affected product was provided in 24/23 cases. In 34/34 cases manufacturers provided information to mitigate product related risks. Requests to pass FSN to persons needing awareness were found in 10/14 cases. Contact data were provided in 30/30 cases. Confirmation that the Competent Authority was informed was found in 12/14 cases and in 19/18 cases a customer confirmation was included. The obtained data suggest that there is an increasing annual number of FSCA and most FSN fulfill the criteria of MEDDEV 2.12-1 rev 8. However, there are differences between German and English FSN, e.g. regarding the distribution to persons needing awareness, missing statement that the Competent Authority was informed and missing customer confirmation. Due to the importance of FSN for reduction of product related risks in FSCA type and content of FSN should be further improved.

Aerosol Use in the Pulmonary Function Lab.

Aerosolized medications are frequently used in the pulmonary function laboratory. The 2 most common implementations are bronchodilators and bronchial challenge agents. Bronchodilator administration is not well standardized, largely because of the various methods of delivery available for clinical practice. Metered-dose inhalers used with spacer devices are the most common route for bronchodilator administration, but many laboratories use small-volume nebulizers. Interpretation of pre- and post-bronchodilator studies is confounded by the definitions of airway obstruction and bronchodilator responsiveness. Protocols for administering bronchial challenge aerosols (methacholine, mannitol, hypertonic saline) are well defined but are susceptible to some of the same problems that limit comparison of bronchodilator techniques. Bronchial challenges with inhaled aerosols are influenced not only by the delivery device but by the patient's breathing pattern, particularly in protocols that include deep inspiratory efforts.

Gaps in capacity for respiratory care in developing countries. Nigeria as a case study.

There are unmet needs for respiratory medical care in developing countries. We sought to evaluate the quality and capacity for respiratory care in low- and lower-middle-income countries, using Nigeria as a case study. We obtained details of the respiratory practice of consultants and senior residents (fellows) in respiratory medicine in Nigeria via a semistructured questionnaire administered to physician attendees at the 2013 National Congress of the Nigerian Thoracic Society. Out of 76 society-registered members, 48 attended the congress, 40 completed the questionnaire, and 35 provided complete data (73% adjusted response rate). Respondents provided information on the process and costs of respiratory medicine training and facility, equipment, and supply capacities at the institutions they represented. Approximately 83% reported working at a tertiary level (teaching) hospital; 91% reported capacity for sputum smear analysis for acid alcohol-fast bacilli, 37% for GeneXpert test cartridges, and 20% for BACTEC liquid sputum culture. Only 34% of respondents could perform full spirometry on patients, and none had the capacity for performing a methacholine challenge test or for measuring the diffusion capacity for carbon monoxide. We estimated the proportion of registered respiratory physicians to the national population at 1 per 2.3 million individuals. Thirteen states with an estimated combined population of 57.7 million offer no specialist respiratory services. Barriers to development of this capacity include the high cost of training. We conclude that substantial gaps exist in the capacity and quality of respiratory care in Nigeria, a pattern that probably mirrors most of sub-Saharan Africa and other countries of similar economic status. Health policy makers should address these gaps systematically.

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.

Anesthesia for bronchoscopy.

Bronchoscopic procedures are at times intricate and the patients often very ill. These factors and an airway shared with the pulmonologist present a clear challenge to anesthesiologists. The key to success lies in the understanding of both the underlying pathology and procedure being performed combined with frequent two-way communication between the anesthesiologist and the pulmonologist. Above all, vigilance and preparedness are paramount. Topics discussed in this review include anesthesia for advanced diagnostic procedures as well as for interventional/ therapeutic procedures. The latter includes bronchoscopic tracheal balloon dilation, tracheobronchial stenting, endobronchial electrocautery, bronchoscopic cryotherapy and other techniques. Special situations, such as tracheoesophageal fistula and mediastinal masses, are also considered.

The role of rigid and flexible bronchoscopy in children.

Bronchoscopy for paediatric respiratory disease is a routine procedure in paediatric pulmonology. Rigid bronchoscopy is now much less commonly used than flexible bronchoscopy. Technological advances have brought better picture quality and easier storage of video documentation. Indications with clear clinical benefit are congenital or acquired unexplained airway obstruction. In pulmonary infections or infiltrates in immunodeficient or immunosuppressed children not responding to empirical treatment a pathogen may be identified by bronchoscopy and bronchoalveolar lavage (BAL). Bronchoscopy and BAL can be indicated in children with unusual presentations of chronic cough or wheeze, and cystic fibrosis. The use of transbronchial biopsies (TBB) is established in paediatric lung transplantation. New applications and techniques are being developed, such as endobronchial ultrasound and transbronchial needle biopsy of lymph nodes and the role of airway stent placement have become better understood.

Performance of an automated electronic acute lung injury screening system in intensive care unit patients.

OBJECTIVE: Lung protective ventilation reduces mortality in patients with acute lung injury, but underrecognition of acute lung injury has limited its use. We recently validated an automated electronic acute lung injury surveillance system in patients with major trauma in a single intensive care unit. In this study, we assessed the system's performance as a prospective acute lung injury screening tool in a diverse population of intensive care unit patients. DESIGN: Patients were screened prospectively for acute lung injury over 21 wks by the automated system and by an experienced research coordinator who manually screened subjects for enrollment in Acute Respiratory Distress Syndrome Clinical Trials Network (ARDSNet) trials. Performance of the automated system was assessed by comparing its results with the manual screening process. Discordant results were adjudicated blindly by two physician reviewers. In addition, a sensitivity analysis using a range of assumptions was conducted to better estimate the system's performance. SETTING: The Hospital of the University of Pennsylvania, an academic medical center and ARDSNet center (1994-2006). PATIENTS: Intubated patients in medical and surgical intensive care units. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 1270 patients screened, 84 were identified with acute lung injury (incidence of 6.6%). The automated screening system had a sensitivity of 97.6% (95% confidence interval, 96.8-98.4%) and a specificity of 97.6% (95% confidence interval, 96.8-98.4%). The manual screening algorithm had a sensitivity of 57.1% (95% confidence interval, 54.5-59.8%) and a specificity of 99.7% (95% confidence interval, 99.4-100%). Sensitivity analysis demonstrated a range for sensitivity of 75.0-97.6% of the automated system under varying assumptions. Under all assumptions, the automated system demonstrated higher sensitivity than and comparable specificity to the manual screening method. CONCLUSIONS: An automated electronic system identified patients with acute lung injury with high sensitivity and specificity in diverse intensive care units of a large academic medical center. Further studies are needed to evaluate the effect of automated prompts that such a system can initiate on the use of lung protective ventilation in patients with acute lung injury.

The use of the Active Breathing Coordinator throughout radical non-small-cell lung cancer (NSCLC) radiotherapy.

PURPOSE: To assess feasibility and reproducibility of an Active Breathing Coordinator (ABC) used throughout radical radiotherapy for non-small-cell lung cancer, and compare lung dosimetric parameters between free-breathing and ABC plans. METHODS AND MATERIALS: A total of 18 patients, recruited into an approved study, had free-breathing and ABC breath-hold treatment plans generated. Lung volume, the percentage volume of lung treated to a dose of ≥20 Gy (V(20)), and mean lung dose (MLD) were compared. Treatment (64 Gy in 32 fractions, 5 days/week) was delivered in breath-hold. Repeat breath-hold computed tomography scans were used to assess change in gross tumor volume (GTV) size and position. Setup error was also measured and potential GTV-planning target volume (PTV) margins calculated. RESULTS: Seventeen of 18 patients completed radiotherapy using ABC daily. Intrafraction tumor position was consistent, but interfraction variation had mean (range) values of 5.1 (0-25), 3.6 (0-9.7), and 3.5 (0-16.6) mm in the superoinferior (SI), right-left (RL), and anteroposterior (AP) directions, respectively. Tumor moved partially outside the PTV in 5 patients. Mean reduction in GTV from planning to end of treatment was 25% (p = 0.003). Potentially required PTV margins were 18.1, 11.9, and 11.9 mm in SI, RL, and AP directions. ABC reduced V(20) by 13% (p = 0.0001), V(13) by 12% (p = 0.001), and MLD by 13% (p < 0.001) compared with free-breathing; lung volume increased by 41% (p < 0.001). CONCLUSIONS: Clinically significant movements of GTV were seen during radiotherapy for non-small-cell lung cancer using ABC. Image guidance is recommended with ABC. The use of ABC can reduce dose volume parameters determining lung toxicity, and might allow for equitoxic radiotherapy dose escalation.