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Background: Interstitial lung diseases (ILD) are poorly understood disorders characterised by diffuse damage to the lung parenchyma, with inflammation and fibrosis. Some manifest a progressive fibrotic phenotype with high fatality and limited treatment options, such as idiopathic pulmonary fibrosis (IPF)., Summary: The degree to which inflammation plays a role in fibrosis progression is unknown. However, wound healing and fibrosis are intricate processes influenced by various inflammatory factors. Extracellular nucleosides and nucleotides, including adenosine triphosphate (ATP), activate pro-inflammatory responses of innate immunity and are widely implicated in tissue fibrosis across different organs. The pro-inflammatory effects of extracellular nucleotides occur via P1 and P2 purinergic receptors, expressed across the lung and immune system, and have been implicated in various pulmonary diseases including pulmonary fibrosis. This review amalgamates available data on the complex role of P1 and P2 purinergic receptor signalling in pulmonary fibrosis and discusses perspectives for novel treatments., Key Messages: Purinergic signalling plays a complex and pivotal role in pulmonary fibrosis, warranting further study. The intricate interplay between P1 and P2 receptor pathways necessitates a comprehensive approach to understand their collective impact. While evidence from preclinical models is promising, human studies are essential for further understanding in pulmonary fibrosis. Advances in receptor-specific agonists and antagonists provide novel avenues for research and may ultimately lead to new therapies for patients., (The Author(s). Published by S. Karger AG, Basel.)

Background: 18F-Fluorodeoxyglucose (FDG) PET/CT is emerging as a tool in the diagnosis and evaluation of pulmonary sarcoidosis, however, there is limited consensus regarding its diagnostic performance and prognostic value., Method: A meta-analysis was conducted with PubMed, Science Direct, MEDLINE, Scopus, and CENTRAL databases searched up to and including September 2023. 1355 studies were screened, with seventeen (n = 708 patients) suitable based on their assessment of the diagnostic performance or prognostic value of FDG-PET/CT. Study quality was assessed using the QUADAS-2 tool. Forest plots of pooled sensitivity and specificity were generated to assess diagnostic performance. Pooled changes in SUVmax were correlated with changes in pulmonary function tests (PFT)., Results: FDG-PET/CT in diagnosing suspected pulmonary sarcoidosis (six studies, n = 400) had a pooled sensitivity of 0.971 (95%CI 0.909-1.000, p = < 0.001) and specificity of 0.873 (95%CI 0.845-0.920)(one study, n = 169). Eleven studies for prognostic analysis (n = 308) indicated a pooled reduction in pulmonary SUVmax of 4.538 (95%CI 5.653-3.453, p = < 0.001) post-treatment. PFTs displayed improvement post-treatment with a percentage increase in predicted forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO) of 7.346% (95%CI 2.257-12.436, p = 0.005) and 3.464% (95%CI -0.205-7.132, p = 0.064), respectively. Reduction in SUVmax correlated significantly with FVC (r = 0.644, p < 0.001) and DLCO (r = 0.582, p < 0.001) improvement., Conclusion: In cases of suspected pulmonary sarcoidosis, FDG-PET/CT demonstrated good diagnostic performance and correlated with functional health scores. FDG-PET/CT may help to guide immunosuppression in cases of complex sarcoidosis or where treatment rationalisation is needed., Clinical Relevance Statement: FDG-PET/CT has demonstrated a high diagnostic performance in the evaluation of suspected pulmonary sarcoidosis with radiologically assessed disease activity correlating strongly with clinically derived pulmonary function tests., Key Points: In diagnosing pulmonary sarcoidosis, FDG-PET/CT had a sensitivity and specificity of 0.971 and 0.873, respectively. Disease activity, as determined by SUVmax, reduced following treatment in all the included studies. Reduction in SUVmax correlated with an improvement in functional vital capacity, Diffusion Capacity of the Lungs for Carbon Monoxide, and subjective health scoring systems., (© 2024. The Author(s).)

Background and Objective: There is increasing interest in the role of lipids in processes that modulate lung fibrosis with evidence of lipid deposition in idiopathic pulmonary fibrosis (IPF) histological specimens. The aim of this study was to identify measurable markers of pulmonary lipid that may have utility as IPF biomarkers., Study Design and Methods: IPF and control lung biopsy specimens were analysed using a unbiased lipidomic approach. Pulmonary fat attenuation volume (PFAV) was assessed on chest CT images (CT PFAV ) with 3D semi-automated lung density software. Aerated lung was semi-automatically segmented and CT PFAV calculated using a Hounsfield-unit (-40 to -200HU) threshold range expressed as a percentage of total lung volume. CT PFAV was compared to pulmonary function, serum lipids and qualitative CT fibrosis scores., Results: There was a significant increase in total lipid content on histological analysis of IPF lung tissue (23.16 nmol/mg) compared to controls (18.66 mol/mg, p = 0.0317). The median CT PFAV in IPF was higher than controls (1.34% vs. 0.72%, p < 0.001) and CT PFAV correlated significantly with DLCO% predicted (R 2  = 0.356, p < 0.0001) and FVC% predicted (R 2  = 0.407, p < 0.0001) in patients with IPF. CT PFAV correlated with CT features of fibrosis; higher CT PFAV was associated with >10% reticulation (1.6% vs. 0.94%, p = 0.0017) and >10% honeycombing (1.87% vs. 1.12%, p = 0.0003). CT PFAV showed no correlation with serum lipids., Conclusion: CT PFAV is an easily quantifiable non-invasive measure of pulmonary lipids. In this pilot study, CT PFAV correlates with pulmonary function and radiological features of IPF and could function as a potential biomarker for IPF disease severity assessment., (© 2023 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

Purpose: Wear of ceramic orthopedic devices generates nanoparticles in vivo that may present a different biological character from the monolithic ceramic from which they are formed. The current work investigated protein adsorption from human plasma on alumina nanoparticles and monolithic samples representative of both wear particles and the ceramic components as implanted., Materials and Methods: A physicochemical characterization of the particles and their dispersion state was carried out, and the protein adsorption profiles were analyzed using 1D SDS-PAGE and mass spectrometry., Results: Significant differences in protein-binding profiles were identified where the nanoparticles selectively bound known transporter proteins rather than the more highly abundant serum proteins that were observed on the monoliths., Conclusions: Proteins associated with opsonization of particles were seen to be present in the protein corona of the nanoparticles, which raises questions regarding the role of wear particles in periprosthetic tissue inflammation and aseptic loosening.

Introduction: Since 2000 a decline in the incidence of occupational asthma (OA) has been reported in the UK and Europe. We aimed to describe and account for trends in the incidence of OA in the West Midlands, UK using annual notification data from the SHIELD voluntary surveillance scheme over the period 1991-2011., Methods: All notifications to the SHIELD database between January 1991 and December 2011 were identified, along with patients' demographic data, occupations, causative agents and confirmatory tests. Annual notifications were scaled to give an annual count per million workers, giving a measure of incidence, and also standardised against those of bakers' asthma. Non-parametric analyses were undertaken between annual incidence and time (years) for common causative agents using (1) a negative binomial regression univariate model and (2) a logistic regression model calculating annual reporting ORs. A step-change analysis was used to examine time points at which there were marked reductions in incidence., Results: A decrease in annual incidence of OA was observed over the study period (incident rate ratio=0.945; 95% CI 0.933 to 0.957; p<0.0001), an effect that was lost after standardising for bakers' asthma. Decreases in incidence were seen for most common causative agents, with only cleaning product-related OA increasing over 21 years. Marked fall in incidence was seen in 2004 for isocyanates, and in 1995 for latex. Most notifications came from a regional specialist occupational lung disease unit, with notifications from other sites falling from 16 cases/million workers/annum in 1995 to 0 in 2004., Conclusions: Reporter fatigue and increasing under-recognition of OA are both factors which contribute to the apparent fall in incidence of OA in the West Midlands. There is a future need for interventions that enable health professionals to identify potential cases of OA in the workplace and in healthcare settings., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Although high-volume bronchoalveolar lavage (BAL) is an excellent research tool, its use in the evaluation of interstitial lung disease remains controversial, particularly in the age of lung biopsy in video-assisted thoracic surgery. Recently, a new practice guideline made several important recommendations for the performance of the procedure and the handling, processing, and analysis of samples. Here we describe this recommended technique, our experience performing BAL in 42 patients, and the usefulness of our differential cell count results. We demonstrate that BAL is straightforward and safe to perform and conclude that it may offer valuable data in evaluating interstitial lung disease, particularly in patients with an acute presentation or who are not fit for lung biopsy., (Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Fractional exhaled nitric oxide (FENO) measurements are recommended for the assessment of eosinophilic airway inflammation in asthma. Clinically relevant increases in FENO have been reported 24 h after positive specific inhalational challenge (SIC) tests in occupational asthma. We aimed to determine whether positive SICs could be discriminated from control tests, on the basis of change in FENO., Methods: We reviewed all positive SICs to a variety of agents performed at our institution 2008-2012 and gathered data on age, sex, asthmatic response (immediate/dual/late), smoking status, inhaled corticosteroid usage, and FENO pre- and 24-h postcontrol and positive SIC from each worker. Changes in FENO after positive SICs were compared with control SICs from each worker, by using paired Student's t tests., Results: In 16 workers, negative control challenges were associated with mean changes in FENO of 9 % (95 % CI -1.14 to 19.01) or 1.1 ppb (95 % CI -3.59 to 5.84); 2 of 16 (13 %) workers tested showed increases in FENO that were clinically relevant based on recent guidelines. Subsequent positive SICs were associated with mean changes in FENO of 7 % (95 % CI −15.73 to 29.6) or 2.1 ppb (95 % CI -6.07 to 10.19), which were not significantly different to controls; only 2 of 16 (13 %) workers had FENO changes that were clinically relevant., Conclusions: FENO changes above the upper confidence limits of ≥20 % or ≥6 ppb may be considered to be outside the range of normality. However, the majority of workers who had clearly positive SICs to common low molecular weight agents also had no statistically or clinically relevant increase in FENO. Therefore, change in FENO does not predict a positive SIC in this group.

Neutrophil lifespan and function are regulated by hypoxia via components of the hypoxia inducible factor (HIF)/von Hippel Lindau/hydroxylase pathway, including specific roles for HIF-1α and prolyl hydroxylase-3. HIF-2α has both distinct and overlapping biological roles with HIF-1α and has not previously been studied in the context of neutrophil biology. We investigated the role of HIF-2α in regulating key neutrophil functions. Human and murine peripheral blood neutrophils expressed HIF-2α, with expression up-regulated by acute and chronic inflammatory stimuli and in disease-associated inflammatory neutrophil. HIF2A gain-of-function mutations resulted in a reduction in neutrophil apoptosis both ex vivo, through the study of patient cells, and in vivo in a zebrafish tail injury model. In contrast, HIF-2α-deficient murine inflammatory neutrophils displayed increased sensitivity to nitrosative stress induced apoptosis ex vivo and increased neutrophil apoptosis in vivo, resulting in a reduction in neutrophilic inflammation and reduced tissue injury. Expression of HIF-2α was temporally dissociated from HIF-1α in vivo and predominated in the resolution phase of inflammation. These data support a critical and selective role for HIF-2α in persistence of neutrophilic inflammation and provide a platform to dissect the therapeutic utility of targeting HIF-2α in chronic inflammatory diseases.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a fatal progressive interstitial pneumonia. The innate immune system provides a crucial function in the recognition of tissue injury and infection. Toll-like receptor 3 (TLR3) is an innate immune system receptor. We investigated the role of a functional TLR3 single-nucleotide polymorphism in IPF., Objectives: To characterize the effects of the TLR3 Leu412Phe polymorphism in primary pulmonary fibroblasts from patients with IPF and disease progression in two independent IPF patient cohorts. To investigate the role of TLR3 in a murine model of pulmonary fibrosis., Methods: TLR3-mediated cytokine, type 1 IFN, and fibroproliferative responses were examined in TLR3 wild-type (Leu/Leu), heterozygote (Leu/Phe), and homozygote (Phe/Phe) primary IPF pulmonary fibroblasts by ELISA, real-time polymerase chain reaction, and proliferation assays. A murine model of bleomycin-induced pulmonary fibrosis was used in TLR3 wild-type (tlr3(+/+)) and TLR3 knockout mice (tlr3(-/-)). A genotyping approach was used to investigate the role of the TLR3 L412F polymorphism in disease progression in IPF using survival analysis and longitudinal decline in FVC., Measurements and Main Results: Activation of TLR3 in primary lung fibroblasts from TLR3 L412F-variant patients with IPF resulted in defective cytokine, type I IFN, and fibroproliferative responses. We demonstrate increased collagen and profibrotic cytokines in TLR3 knockout mice (tlr3(-/-)) compared with wild-type mice (tlr3(+/+)). TLR3 L412F was also associated with a significantly greater risk of mortality and an accelerated decline in FVC in patients with IPF., Conclusions: This study reveals the crucial role of defective TLR3 function in promoting progressive IPF.

Background: There is a disproportionately high number of cases of work-related asthma occurring in health care occupations due to agents such as glutaraldehyde, latex and cleaning products., Aims: To understand the causes and measure trends over time of occupational asthma (OA) in health care workers (HCWs)., Methods: We reviewed OA notifications from the Midland Thoracic Society's Surveillance Scheme of Occupational Asthma (SHIELD) database in the West Midlands, UK, from 1991 to 2011 and gathered data on occupation, causative agent and annual number of notifications., Results: There were 182 cases of OA in HCWs (median annual notifications = 7; interquartile range [IQR] = 5-11), representing 5-19% of annual SHIELD notifications. The modal annual notification was 20 (in 1996); notifications have declined since then, in line with total SHIELD notifications. The majority of cases (136; 75%) occurred in nursing, operating theatre, endoscopy and radiology staff. The most frequently implicated agents were glutaraldehyde (n = 69), latex (n = 47) and cleaning products (n = 27), accounting for 79% of the 182 cases. Cleaning product-related OA was an emerging cause with 22 cases after 2001 and only 5 cases between 1991 and 2000., Conclusions: Control measures within the UK National Health Service have seen a decline in OA in HCWs due to latex and glutaraldehyde, though OA remains a problem amongst HCWs exposed to cleaning products. Continuing efforts are required to limit the number of cases in this employment sector.

The role of bronchoalveolar lavage (BAL) in the assessment of interstitial lung disease (ILD) remains controversial. Previous studies have demonstrated that BAL cell differential is useful in predicting disease progression in many forms of ILD. We wished to investigate whether BAL had a similar use in predicting disease progression in asbestosis. 21 patients who had significant asbestos exposure, findings of UIP radiologically and BAL performed as part of their investigation were reviewed. There was a significant inverse correlation between percentage BAL neutrophils and percentage predicted DLCO at diagnosis (n=21; P=0.02; r(2)=(-)0.25; CI, (-)0.77(-)0.08), but not with DLCO decline over 1 year. Unlike previous reports in IPF, BAL cell differential is not predictive of decline in classic asbestosis with a UIP pattern and its routine use in this cohort of patients provides little if any additional benefit.

The use of endobronchial stents in the treatment of tumour related tracheobronchial stenosis has been well described. While many forms of stent exist, their use has invariably been described in the context of rigid bronchoscopy and general anaesthesia. Few reports exist on the use of endobronchial stents for the treatment of thyroid goitre related stenosis.Our objective was to retrospectively analyse the use of self expanding metal stent (SEMS) insertion for thyroid related tracheobronchial stenosis under sedation with flexible bronchoscopy in the treatment of this condition. Patient charts were reviewed on all patients who had stent insertion in our unit since 1999-2005. We analysed the indication for stenting, pathology, stent size and location and detail any complications of therapy. Particular attention was paid to those with benign disease to evaluate the recommendation made by the U.S Food and Drug Administration (FDA) in 2005 on the use of metal stents in benign airways disease. A total of five patients (4 female, 1 male) who were too unfit for surgery had stent insertion for thyroid related tracheobronchial stenosis over this period. All patients experienced complications which became prolonged and recurrent in those with benign disease who survived longer. We conclude that SEMS insertion via flexible bronchoscopy is not appropriate for the treatment of benign thyroid goitre related tracheobronchial stenosis until all other interventions have been exhaustively explored.

Background: Occupational asthma (OA) remains common; 1 in 10 cases of adult-onset asthma is due to work. Health outcomes are better with early diagnosis, but there is considerable delay, largely due to lack of enquiry about work effect in primary care. National guidelines (2008) recommend asking two screening questions, which together have a high sensitivity in identifying OA., Aims: To audit how working-age asthmatics are currently screened for OA in a local primary care population., Methods: An audit of the electronic patient records of working-age asthmatics, from four Birmingham primary care practices was undertaken. Practice-level data (list size, gender, prevalence of asthma and OA and socio-economic status) and patient-level data (gender, age, onset, occupation and work-effect enquiry and lung function) were collected., Results: The total practice population was 27,295 of which 17,564 (64%) were of working age. The audit sample was 396 of whom 49% were male. The prevalence of asthma in working-age adults was 12% (8-15%) and the prevalence of OA in working-age asthmatics was 0.3% (0-0.8%). Occupation was recorded in only 55/396 (14%) cases with very few (2) documented within the asthma-review template. Occupation was only recorded in 13/55 adult-onset asthmatics in high-risk occupations. Of 396, 9 (2%) had any work-effect enquiry and 4 patients had work-effect enquiry at diagnosis in those with traceable notes (n = 117)., Conclusions: The prevalence of OA was low, suggesting under-diagnosis plus under-reporting in primary care. Occupation and work-effect enquiry is lacking despite guidelines for identifying OA. Existing electronic templates for recording asthma review could be modified to include these elements.

Background: The death receptor ligand tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) shows considerable clinical promise as a therapeutic agent. TRAIL induces leukocyte apoptosis, reducing acute inflammatory responses in the lung. It is not known whether TRAIL modifies chronic lung injury or whether TRAIL has a role in human idiopathic pulmonary fibrosis (IPF). We therefore explored the capacity of TRAIL to modify chronic inflammatory lung injury and studied TRAIL expression in patients with IPF., Methods: TRAIL(-/-) and wild-type mice were instilled with bleomycin and inflammation assessed at various time points by bronchoalveolar lavage and histology. Collagen deposition was measured by tissue hydroxyproline content. TRAIL expression in human IPF lung samples was assessed by immunohistochemistry and peripheral blood TRAIL measured by ELISA., Results: TRAIL(-/-) mice had an exaggerated delayed inflammatory response to bleomycin, with increased neutrophil numbers (mean 3.19±0.8 wild type vs 11.5±5.4×10(4) TRAIL(-/-), p<0.0001), reduced neutrophil apoptosis (5.42±1.6% wild type vs 2.47±0.5% TRAIL(-/-), p=0.0003) and increased collagen (3.45±0.2 wild type vs 5.8±1.3 mg TRAIL(-/-), p=0.005). Immunohistochemical analysis showed induction of TRAIL in bleomycin-treated wild-type mice. Patients with IPF demonstrated lower levels of TRAIL expression than in control lung biopsies and their serum levels of TRAIL were significantly lower compared with matched controls (38.1±9.6 controls vs 32.3±7.2 pg/ml patients with IPF, p=0.002)., Conclusion: These data suggest TRAIL may exert beneficial, anti-inflammatory actions in chronic pulmonary inflammation in murine models and that these mechanisms may be compromised in human IPF.

Objective: To describe a 10-year experience of inserting Ultraflex™ self-expanding metal stents (SEMS) under sedation using flexible bronchoscopy for the treatment of malignant tracheobronchial stenosis in a tertiary referral centre., Methods: Medical notes were retrospectively reviewed for all patients who underwent SEMS insertion between 1999 and 2009., Results: A data analysis of 68 patients who had Ultraflex™ SEMS inserted under sedation was completed. Thirty three males and 35 females with a mean age of 67.9 years (range 35-94) presented with features including dyspnea/respiratory distress (39 patients), stridor (16 patients) and hemoptysis/dyspnea (13 patients). Etiology of stenosis included lung cancer (46 patients) esophageal cancer (14 patients) and other malignancies (8 patients). Mean dose of midazolam administered was 5mg (range 0-10mg). The trachea was the most common site of stent insertion followed by the right and left main bronchus, respectively. Adjuvant laser therapy was applied at some stage in 31% of all cases, and chemotherapy and/or radiotherapy was administered to at least 64% of patients with malignant disease. Hemoptysis and stent migration were the most frequent complications (5 and 4 patients, respectively). The mean survival time of stented non-small cell lung cancer (NSCLC) patients was 214 days (range 5-1233) and that of esophageal malignancy was 70 days (range 12-249). Mean pack-year history of individuals with lung cancer requiring stent insertion was 37 (range 2-100)., Conclusion: Ultraflex stents offer a safe and effective therapy for patients who are inoperable or unresectable that otherwise would have no alternative therapy. It has an immediate beneficial effect upon patients, not only through symptom relief but, in some, through prolongation of life. Survival data is no worse than other studies using different varieties of stents and insertion techniques indicating its longer-term efficacy. Moreover, this report highlights the feasibility of performing this procedure successfully in a respiratory unit, without the need for general anesthesia., (Copyright © 2011 SEPAR. Published by Elsevier Espana. All rights reserved.)

Novel therapeutics targeting neutrophilic inflammation are a major unmet clinical need in acute and chronic inflammation. The timely induction of neutrophil apoptosis is critical for inflammation resolution, and it is thought that acceleration of apoptosis may facilitate resolution at inflammatory sites. We previously demonstrated that a death receptor ligand, TRAIL, accelerates neutrophil apoptosis in vitro. We examined the role of TRAIL in neutrophil-dominant inflammation in WT and TRAIL-deficient mice. TRAIL deficiency did not alter constitutive neutrophil apoptosis, whereas exogenous TRAIL accelerated apoptosis of murine peripheral blood neutrophils. We compared TRAIL-deficient and WT mice in two independent models of neutrophilic inflammation: bacterial LPS-induced acute lung injury and zymosan-induced peritonitis. In both models, TRAIL-deficient mice had an enhanced inflammatory response with increased neutrophil numbers and reduced neutrophil apoptosis. Correction of TRAIL deficiency and supraphysiological TRAIL signaling using exogenous protein enhanced neutrophil apoptosis and reduced neutrophil numbers in both inflammatory models with no evidence of effects on other cell types. These data indicate the potential therapeutic benefit of TRAIL in neutrophilic inflammation.

Background: Interventional pulmonology, in particular, tracheobronchial stent insertion, has been well described in the treatment of tracheobronchial malignant disease. Its benefits are particularly obvious in patients with inoperable malignancy or in those unfit for surgery and have been extensively described. Fewer data exist on the benefits of using self-expanding metal stents (SEMS) inserted via flexible bronchoscopy in the treatment of tracheobronchial stenosis due to extrinsic compression or infiltration from primary oesophageal malignancy., Methods: We retrospectively reviewed all patients who had stent insertion via flexible bronchoscopy from 2002 to 2010 at our institution., Results: We found 14 patients who had Ultraflex™ self-expanding metal stent insertion for this condition. We analysed this group of patients with respect to their presentation; indications for stent insertion over surgery; size, location, and number of stents inserted; sedative dose; complications of therapy; and survival time., Conclusion: We conclude that insertion of SEMS via flexible bronchoscopy is a safe and effective therapy for those individuals who require palliation or are too unfit for the general anaesthesia required for surgery. Moreover, this form of stent insertion may be performed by respiratory physicians in the bronchoscopy suite, rather than by their cardiothoracic counterparts in theatre.

In most diseases related to pleural effusion, the fluid analysis yields important diagnostic information, and in certain cases, fluid analysis alone is enough for diagnosis. The many important characteristics of pleural fluid are described, as are other complementary investigations that can assist with the diagnosis of common and rare pleural effusions. For a systematic review of pleural effusion, a literature search for articles on the practical investigation and diagnosis of pleural effusion was done. Articles included guidelines, expert opinion, experimental and nonexperimental studies, literature reviews, and systematic reviews published from May 2003 through June 2009. The search yielded 1 guideline, 2 meta-analyses, 9 literature reviews, 1 randomized control trial, and 9 clinical studies. On the basis of class IIa or class I evidence from these articles, a step by step approach is recommended for investigating a pleural effusion, beginning with assessment of the medical history, clinical examination, radiology, pleural fluid evaluation, and finally, if no diagnosis is forthcoming, a pleural biopsy under image guidance or thoracoscopy.

Mycobacterium tuberculosis (TB) infection of the pleural space is an important cause of pleural effusion in areas of high TB prevalence. Microbiological analyses of pleural fluid in the acute setting may be negative. Consequently, investigations may proceed to more invasive techniques, such as pleural biopsy or thoracoscopy. Ongoing research has led to implementing a number of additional fluid analyses that may lead to a diagnosis without a need for further invasive procedures. In this review, we discuss the characteristics of tuberculous pleural fluid that may assist in this important diagnosis, and we highlight the benefits of specific biomarker analyses. English-language publications from a MEDLINE search and references from relevant articles from January 1, 1990 to September 1, 2009 were reviewed. The key words searched included tuberculosis, pleural fluid, effusion, diagnosis, adenosine deaminase, and interferon., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Non-tuberculous mycobacteria (NTM) are a group of alcohol fast, aerobic, nonmotile bacteria that are found in the environment. Recent reports indicate that their incidence and prevalence is increasing and guidelines have been developed laying down criteria for diagnosis. The treatment of these mycobacteria may be difficult, in many cases involving complex regimens containing multiple drugs. While traditional anti-tuberculosis medications are frequently used, specific therapeutic regimens depend on the organism isolated, in vitro susceptibility testing, drug tolerance and toxicity and concomitant medical disorders. In this review, we describe the diagnosis and treatment of the more important lung pathogens, describing complexities and controversies surrounding treatment with traditional, adjunctive and the newer and more experimental agents., (Copyright 2010 Elsevier Ltd. All rights reserved.)

The investigation of pleural effusion has been greatly assisted by advancements in pleural fluid analysis. In the case of tuberculous pleural effusion, diagnosis traditionally requires the demonstration of acid fast bacilli in the pleural space using microbiological or histological techniques. In recent years, there has been progress in pleural fluid analysis in suspected tuberculous effusions, with particular interest in adenosine deaminase and interferon-γ. These individual tests are quite sensitive and specific; however, data are sparse on the benefits that multiple-parameter testing may have when analysed in combination. We reviewed the literature to investigate the evidence for multiple-parameter testing, both biochemical and clinical, in the evaluation of tuberculous effusion.

The investigation of a pleural effusion is, in general, a very straight forward process with the combination of clinical history, examination, radiology and pleural fluid analysis leading to diagnosis in most cases. While most fluid samples are sent for routine analysis including protein, LDH, glucose, cytology and microbiology, there are a number of more unusual fluid analyses available which in some cases directly lead to, and in others are suggestive of the diagnosis. Moreover, other fluid markers are constantly being evaluated as a diagnostic tool. In this review, we describe these non-routine pleural fluid analyses in detail. English language publications in MEDLINE and references from relevant articles from January 1 1990 to August 1 2009 were reviewed. Keywords searched in combination were pleural fluid, effusion, analysis, transudate, exudate and diagnosis., (Copyright 2010 Elsevier Ltd. All rights reserved.)

Nontuberculous mycobacteria (NTM) are resilient bacteria that grow in virtually any environment, especially those where competing microorganisms are destroyed, such as in chlorinated water. They have been discovered in soil, dust, food, water, and domestic and wild animals. Nontuberculous mycobacteria tend to infect individuals with local (e.g., damaged skin or lung) or systemic (e.g., HIV, drugs, malignancy) defects in host defence, and their incidence and prevalence have consistently increased in the last decade. Difficulty may arise in determining whether an isolated NTM from a microbiological sample is in fact a contaminant or a pathogenic organism. In this review, we discuss the important mycobacteria involved in lung disease, factors that predispose individuals to infection, and their diagnosis and treatment according to updated guidelines. English language publications in MEDLINE and references from relevant articles from January 1, 1990 to June 28, 2009 were reviewed. Keywords searched were "nontuberculous,""mycobacteria," "diagnosis," and "treatment."

Chylothorax is a rare condition that results from thoracic duct damage with chyle leakage from the lymphatic system into the pleural space, usually on the right side. It has multiple aetiologies and is usually discovered after it manifests itself as a pleural effusion. Diagnosis involves cholesterol and triglyceride measurement in the pleural fluid. Complications include malnutrition, immunosuppression and respiratory distress. Treatment may be either conservative or aggressive depending on the clinical scenario. In this review, we discuss the aetiology, diagnosis and treatment of chylothorax. English language publications in MEDLINE and references from relevant articles from January 1, 1980 to February 28, 2008 were reviewed. Keywords searched were chylothorax, aetiology, diagnosis and treatment., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Fluid in the pleural space is a common sequela of a wide range of diseases which may be pulmonary, pleural or extrapulmonary. As the differential diagnosis is wide, a systematic approach to investigation and diagnosis is recommended. This review highlights the important features and recommendations for the investigation of a unilateral pleural effusion, a common condition encountered by the general physician. The aim of this study was to assist with a speedy diagnosis of the underlying pathology, using appropriate investigative techniques, while minimising the use of invasive procedures.

An association between Mycobacterium malmoense and underlying lung disease has been described. The purpose of this study was to further explore this relationship and in particular to identify any relationship between Coal Workers' Pneumoconiosis (CWP) and M. malmoense infection. Patient charts were reviewed of all patients who had a positive sputum or bronchoalveolar lavage for M. malmoense from 1999 to 2006 in a large district general hospital in South Yorkshire, UK. We also performed a literature review in search of this association; one case report was found. Four patients had positive sputum cultures for M. malmoense but only three of these fulfilled the ATS 1997 criteria for diagnosis of disease. Of these three patients, all had clinical and radiologic evidence of CWP. This study strengthens the evidence of a link between nontuberculous mycobacteria and underlying lung disease but more importantly highlights an association between M. malmoense and CWP which has been rarely reported and is poorly understood.

While the prevalence of Mycobacterium tuberculosis continues to decline in the developed world, the same cannot be said for non-tuberculous mycobacteria (NTM). These organisms are increasing in incidence and prevalence throughout the world. This is probably because of a combination of increased exposure, improved diagnostic methods and an increase in the prevalence of risk factors that predispose individuals to infection. Considerable confusion can arise in determining in the wide range of species whether an isolated NTM is in fact a contaminant or a pathogenic organism when isolated in sputum or bronchoalveolar lavage. This confusion combined with increasing requests for advice on the treatment of disease has led to the development of guidelines to assist the clinician in diagnosing and treating infection accurately.