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Adjustable maintenance dosing permits patients to increase or decrease their medication, according to a management plan, in response to daily variations in asthma. Adjustable maintenance dosing with budesonide/formoterol in a single inhaler was compared with fixed dosing bid in eight randomised, open-label studies. Data on resource utilisation were collected prospectively in six of the studies. Duration of randomised treatment was 3 months (UK, Italy, Germany), 4 months (Belgium), 5 months (Canada) or 6 months (Sweden). Mean number of budesonide/formoterol inhalations/day was significantly lower for adjustable maintenance dosing vs. fixed dosing, which resulted in significantly lower drug and total costs with adjustable maintenance dosing vs. fixed-dosing group. In the 3- and 4-month studies, both regimens had similar effectiveness. In the Canadian and Swedish studies, a significantly lower percentage of adjustable maintenance dosing patients had asthma exacerbations compared with fixed dosing. Adjustable maintenance dosing reduced treatment costs, providing similar or better asthma control at a lower overall dose, compared with fixed dosing. [ABSTRACT FROM AUTHOR]

Plasma histamine concentration was measured in venous blood draining the site of antigen-induced wheal and flare responses in the forearm skin of seven atopic volunteers. Concentrations were measured using a double isotope radioenzymatic method. The mean +/- s.e. mean resting plasma concentration was 0.18 +/- 0.01 ng/ml. In all subjects an increase was detected in local plasma histamine concentration after intradermal antigen challenge. The peak histamine concentration occurred between 2 and 15 min after challenge, and represented an increase of three- to 20-fold above the resting concentration. Plasma histamine concentration remained significantly elevated for at least 60 min after challenge. A 30 min incubation at 37 degrees C of blood taken at the time of peak plasma concentration caused a fall in histamine concentration. This suggests that histamine release from basophils during the sampling procedure was not a significant problem. This method is less invasive than skin chamber or blister techniques for the demonstration of mediator release in cutaneous inflammation and allows a simultaneous assessment of tissue response. [ABSTRACT FROM AUTHOR]

E-cigarette or vaping product use-associated lung injury is a recently recognised, acute pulmonary syndrome which has been reported (particularly from June to October 2019) throughout the USA, but not in Europe (although one probable case, in the UK, has been reported; Medicines and Healthcare products Regulatory Agency, 2020). It presents acutely, most often in young men, as severe pulmonary consolidation, usually with respiratory failure. The mortality is around 2%. The cause(s) are unknown, but it is associated with vaping, particularly using unlicensed cannabis-containing products with tetrahydrocannabinol. Vitamin E acetate, often present in tetrahydrocannabinol-containing vape products as a solvent, has been implicated, as it has been identified in the bronchoalveolar lavage fluid of patients with e-cigarette or vaping product use-associated lung injury. This article reviews the recent literature, including clinical features, presentation and investigations, and possible mechanisms, in the context of vaping practices in the USA and the UK.

Increasing cannabis use and legalisation highlights the paucity of data we have on the safety of cannabis smoking for respiratory health. Unfortunately, concurrent use of tobacco among marijuana smokers makes it difficult to untangle individual effect of marijuana smoking. Chronic cannabis only smoking has been shown in large cohort studies to reduce forced expiratory volume in 1 s/forced vital capacity via increasing forced vital capacity in chronic use contrary to the picture seen in tobacco smoking. The cause of this is unclear and there are various proposed mechanisms including respiratory muscle training secondary to method of inhalation and acute anti-inflammatory effect and bronchodilation of cannabis on the airways. While cannabis smoke has been shown to increase symptoms of chronic bronchitis, it has not been definitively shown to be associated with shortness of breath or irreversible airway changes. The evidence surrounding the development of lung cancer is less clear; however, preliminary evidence does not suggest association. Bullous lung disease associated with marijuana use has long been observed in clinical practice but published evidence is limited to a total of 57 published cases and only one cross-sectional study looking at radiological changes among chronic users which did not report any increase in macroscopic emphysema. More studies are required to elucidate these missing points to further guide risk stratification, clinical diagnosis and management., Key Points: Cannabis smoking has increased and is likely to increase further with relaxation of legalisation and medicinal use of cannabinoids.Chronic marijuana smoking often produces symptoms similar to those of chronic tobacco smoking such as cough, sputum production, shortness of breath and wheeze.Cessation of marijuana smoking is associated with a reduction in respiratory symptoms and no increased risk of chronic bronchitis.Spirometry changes seen in chronic marijuana smokers appear to differ from those in chronic tobacco smokers. In chronic marijuana smokers there is an increase in FVC as opposed to a definite decrease in FEV 1 .Multiple case series have demonstrated peripheral bullae in marijuana smokers, but no observational studies have elucidated the risk.There is currently no clear association between cannabis smoking and lung cancer, although the research is currently limited., Educational Aims: To update readers on legalisation of recreational and medicinal cannabis.To summarise the evidence base surrounding the respiratory effects of inhaled marijuana use.To provide clinicians with an understanding of the main differences between cannabis and tobacco to be able to apply this to patient education.To highlight common respiratory problems among cannabis users and the need for recreational drug history taking., Competing Interests: Conflict of interest: None declared.

As cannabis use increases, physicians need to be familiar with the effects of both cannabis and tobacco on the lungs. However, there have been very few long-term studies of cannabis smoking, mostly due to legality issues and the confounding effects of tobacco. It was previously thought that cannabis and tobacco had similar long-term effects as both cause chronic bronchitis. However, recent large studies have shown that, instead of reducing forced expiratory volume in 1 s and forced vital capacity (FVC), marijuana smoking is associated with increased FVC. The cause of this is unclear, but acute bronchodilator and anti-inflammatory effects of cannabis may be relevant. Bullous lung disease, barotrauma and cannabis smoking have been recognised in case reports and small series. More work is needed to address the effects of cannabis on lung function, imaging and histological changes.

Pulmonary nodule formation is a frequent feature of granulomatosis with polyangiitis (GPA). Traditional induction therapy includes methotrexate or cyclophosphamide, however, pulmonary nodules generally respond slower than vasculitic components of disease. Efficacy of rituximab (RTX) solely for the treatment of pulmonary nodules has not been assessed. In this observational cohort study, we report patient outcomes with RTX in GPA patients with pulmonary nodules who failed to achieve remission following conventional immunosuppression. Patients (n = 5) with persistent pulmonary nodules were identified from our clinic database and retrospectively evaluated. Systemic manifestations, inflammatory markers, disease activity, concurrent immunosuppression, and absolute B cell numbers were recorded pre-RTX and at 6 monthly intervals following treatment. Chest radiographs at each time point were scored by an experienced radiologist, blinded to clinical details. Five patients with GPA and PR3-ANCA were evaluated (2 male, 3 female), mean age 34 (22-52) years. Pulmonary nodules (median 4, range 2-6), with or without cavitation were present in all patients. RTX induced initial B cell depletion (<5 cells/μL) in all patients but re-population was observed in 3 patients. Repeated RTX treatment in these 3 and persistent B cell depletion in the whole cohort was associated with further significant radiological improvement. Radiographic scoring at each time interval showed reduction in both number of nodules (P =  <0.0001) and largest nodule diameter (P =  <0.0001) in all patients for at least 18 months following B cell depletion. In summary, RTX therapy induces resolution of pulmonary granulomatous inflammation in GPA following prolonged B cell depletion.

Background and Purpose: Domiciliary nebulisers are widely used in chronic obstructive pulmonary disease (COPD) but nebuliser cleaning practice has not been assessed in patients with COPD who are often elderly and may have severe disease and multiple comorbidities. We aimed to evaluate microbial contamination of home nebulisers used by patients with COPD., Methods: Random microbiological assessment of domiciliary nebulisers was undertaken together with an enquiry into cleaning practices. We also examined the effectiveness of the trust-wide cleaning instructions in eradicating isolated microorganisms in a laboratory setting., Results: The mean age of patients in this study was 71 (range 40-93) years, and in 68% of patients a large number of significant comorbidities were present. Forty-four nebuliser sets were obtained and 73% were contaminated with microorganisms at >100 colony forming units/plate. Potentially pathogenic bacteria colonised 13 of the 44 nebulisers (30%) and organisms isolated included Pseudomonas aeroginosa, Staphylococcus aureus, multidrug resistant Serratia marcesans, Escherichia coli and multiresistant Klebsiella spp, Enterobacteriaceae and fungus Fusarium oxysporum. Washing of nebuliser masks, chambers and mouthpieces achieved complete eradication of Gram-positive bacterial and fungal flora. Gram-negative organisms were incompletely eradicated, which may be attributed to the presence of biofilms. We also found that in patients with pathogenic organisms cultured on the nebuliser sets, there was a higher probability of occurrence of a COPD exacerbation with a mean number of exacerbations of 3.3 (SD=1) per year in the group in whom pathogens were isolated compared with 1.7 (SD=1.2) exacerbations per year in those whose sets grew non-pathogenic flora (p=0.02)., Conclusions: Nebulisers contaminated with microorganisms are potential reservoirs delivering serious pathogens to the lung. Relationships between nebuliser contamination, clinical infection and exacerbations require further examination, but is a potential concern in elderly patients with COPD with comorbidities who fail to effectively maintain reasonable standards of nebuliser cleanliness.

Objective: We compared the efficacy of noninvasive ventilation with bilevel positive airway pressure added to usual care versus usual care alone in patients undergoing coronary artery bypass grafting., Methods: We performed a 2-group, parallel, randomized controlled trial. The primary outcome was time until fit for discharge. Secondary outcomes were partial pressure of carbon dioxide, forced expiratory volume in 1 second, atelectasis, adverse events, duration of intensive care stay, and actual postoperative stay., Results: A total of 129 patients were randomly allocated to bilevel positive airway pressure (66) or usual care (63). Three patients allocated to bilevel positive airway pressure withdrew. The median duration of bilevel positive airway pressure was 16 hours (interquartile range, 11-19). The median duration of hospital stay until fit for discharge was 5 days for the bilevel positive airway pressure group (interquartile range, 4-6) and 6 days for the usual care group (interquartile range, 5-7; hazard ratio, 1.68; 95% confidence interval, 1.08-2.31; P = .019). There was no significant difference in duration of intensive care, actual postoperative stay, and mean percentage of predicted forced expiratory volume in 1 second on day 3. Mean partial pressure of carbon dioxide was significantly reduced 1 hour after bilevel positive airway pressure application, but there was no overall difference between the groups up to 24 hours. Basal atelectasis occurred in 15 patients (24%) in the usual care group and 2 patients (3%) in the bilevel positive airway pressure group. Overall, 30% of patients in the bilevel positive airway pressure group experienced an adverse event compared with 59% in the usual care group., Conclusions: Among patients undergoing elective coronary artery bypass grafting, the use of bilevel positive airway pressure at extubation reduced the recovery time. Supported by trained staff, more than 75% of all patients allocated to bilevel positive airway pressure tolerated it for more than 10 hours., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Pulmonary renal syndrome (PRS) describes the occurrence of renal failure in association with respiratory failure, characterised by autoimmune-mediated rapidly progressive glomerulonephritis (RPGN) and diffuse alveolar haemorrhage (DAH), respectively. PRS is associated with significant morbidity and mortality, and prompt diagnosis and treatment significantly improve outcomes. Prompt diagnosis of PRS requires a high index of suspicion, as clinical features are non-specific, and immunological testing aids the diagnosis in many cases. The diagnostic evaluation of DAH and RPGN is outlined in the context of the important differential diagnoses. The commonest causes of PRS include antineutrophil cytoplasm antibody (ANCA)-associated vasculitis and antiglomerular basement membrane disease. As such, more emphasis has been placed on these two conditions in addition to an overview of the less common causes of PRS. We provide a practical review of the diagnostic evaluation, current treatment strategies and clinical outcomes of PRS for renal, respiratory and general physicians.

Diffuse alveolar haemorrhage (DAH) is a serious complication of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). A literature review was performed to ascertain the diagnostic features, treatment, and outcome of this rare but serious condition. Haemoptysis and dyspnoea are common but non-specific features. Chest radiography is usually abnormal, and high-resolution computerised tomographic scanning is more sensitive. Increased uptake of inhaled carbon monoxide and reduced clearance of C(15)O on lung function testing is suggestive of intra-alveolar blood. Fiberoptic bronchoscopy and bronchoalveolar lavage are useful when a super-added infection is suspected. Concurrent renal disease is common and contributes to the morbidity and mortality. Treatment should be individualised, and it is based on glucocorticoid and cyclophosphamide induction with azathioprine maintenance. The role of plasmapheresis is unclear, and is currently being evaluated. Patients are at risk of disease and treatment-related long-term complications. Ongoing research into the most efficacious therapeutic regimens associated with the least side effects is especially important.

Reduction in total lung capacity (TLC) in obese men is associated with restricted expansion of the thoracic cavity at full inflation. We hypothesized that thoracic expansion was reduced by the load imposed by increased total trunk fat volume or its distribution. Using MRI, we measured internal and subcutaneous trunk fat and total abdominal and thoracic volumes at full inflation in 14 obese men [mean age: 52.4 yr, body mass index (BMI): 38.8 (range: 36-44) kg/m(2)] and 7 control men [mean age: 50.1 yr, BMI: 25.0 (range: 22-27.5) kg/m(2)]. TLC was measured by multibreath helium dilution and was restricted (<80% of the predicted value) in six obese men (the OR subgroup). All measurements were made with subjects in the supine position. Mean total trunk fat volume was 16.65 (range: 12.6-21.8) liters in obese men and 6.98 (range: 3.0-10.8) liters in control men. Anthropometry and mean total trunk fat volumes were similar in OR men and obese men without restriction (the ON subgroup). Mean total intraabdominal volume was 9.41 liters in OR men and 11.15 liters in ON men. In obese men, reduced thoracic expansion at full inflation and restriction of TLC were not inversely related to a large volume of 1) intra-abdominal or total abdominal fat, 2) subcutaneous fat volume around the thorax, or 3) total trunk fat volume. In addition, trunk fat volumes in obese men were not inversely related to gas volume or estimated intrathoracic volume at supine functional residual capacity. In conclusion, this study failed to support the hypotheses that restriction of TLC or impaired expansion of the thorax at full inflation in middle-aged obese men was simply a consequence of a large abdominal volume or total trunk fat volume or its distribution.

Objectives: ANCA-associated vasculitis and interstitial lung disease (ILD) are uncommon conditions. The occurrence of both diseases in the same patient is increasingly recognized. Our aim was to ascertain the characteristics and outcomes of patients with ILD and ANCA-associated vasculitis., Methods: A retrospective observational cohort study was performed. Patients who presented to the Hammersmith Hospital, London, with ANCA-associated vasculitis [granulomatosis with polyangiitis (Wegener's), microscopic polyangiitis (MPA) or Churg-Strauss syndrome] who also had ILD were included. Following hospital discharge, all patients were followed up in a multi-disciplinary vasculitis clinic. We recorded patient demographics, diagnostic tests, treatment, complications and mortality., Results: ILD was observed in 2.7% (n = 14) of our patients with ANCA-associated vasculitis (n = 510); all had MPO-ANCA and a clinical diagnosis of MPA, giving a prevalence of 7.2% in patients with MPA (n = 194). There was no significant difference in survival between patients with MPA and ILD and those with MPA alone., Conclusion: It is important that physicians are aware of this clinical association and the presence of ILD should be considered in all patients with ANCA-associated vasculitis, especially those with MPO-ANCA. The possibility that patients with ILD may subsequently develop features of systemic vasculitis should also be remembered.

Restriction of total lung capacity (TLC) is found in some obese subjects, but the mechanism is unclear. Two hypotheses are as follows: 1) increased abdominal volume prevents full descent of the diaphragm; and 2) increased intrathoracic fat reduces space for full lung expansion. We have measured total intrathoracic volume at full inflation using magnetic resonance imaging (MRI) in 14 asymptomatic obese men [mean age 52 yr, body mass index (BMI) 35-45 kg/m2] and 7 control men (mean age 50 yr, BMI 22-27 kg/m2). MRI volumes were compared with gas volumes at TLC. All measurements were made with subjects supine. Obese men had smaller functional residual capacity (FRC) and FRC-to-TLC ratio than control men. There was a 12% predicted difference in mean TLC between obese (84% predicted) and control men (96% predicted). In contrast, differences in total intrathoracic volume (MRI) at full inflation were only 4% predicted TLC (obese 116% predicted TLC, control 120% predicted TLC), because mediastinal volume was larger in obese than in control [heart and major vessels (obese 1.10 liter, control 0.87 liter, P=0.016) and intrathoracic fat (obese 0.68 liter, control 0.23 liter, P<0.0001)]. As a consequence of increased mediastinal volume, intrathoracic volume at FRC in obese men was considerably larger than indicated by the gas volume at FRC. The difference in gas volume at TLC between the six obese men with restriction, TLC<80% predicted (OR), and the eight obese men with TLC>80% predicted (ON) was 26% predicted TLC. Mediastinal volume was similar in OR (1.84 liter) and ON (1.73 liter), but total intrathoracic volume was 19% predicted TLC smaller in OR than in ON. We conclude that the major factor restricting TLC in some obese men was reduced thoracic expansion at full inflation.

Objective: We report a patient with a 20-year history of apparently idiopathic airways stenoses, who presented with an antineutrophil cytoplasmic antibody (ANCA) associated, acute, systemic vasculitis with necrotising glomerulonephritis, subsequently diagnosed as Wegener's granulomatosis., Methods: We present a case report and a review of the world literature on airway stenosis in Wegener's granulomatosis., Results: To our knowledge, this is the first report of Wegener's granulomatosis manifesting as local airway disease for such a prolonged period, before transforming into a systemic vasculitis., Conclusions: This case highlights the need for physicians to be alert to the possibility of Wegener's granulomatosis as a cause of apparently idiopathic airway stenosis, and to be aware that systemic disease may occur in very long-standing, limited Wegener's granulomatosis.

Rationale: Oral corticosteroids effectively treat asthma exacerbations but are associated with well-described side effects., Objective: This study compared the efficacy and safety of a high dose of an inhaled corticosteroid with oral prednisolone in patients with worsening of their asthma after medication withdrawal., Methods: Patients tapered off their inhaled corticosteroids until they reached predefined criteria of "worsening asthma". Randomized patients (n=130) were treated double blind with either ciclesonide 800mug twice daily (starting with 800mug hourly for 3h after randomization) or prednisolone 40mg once daily for 2 weeks. Spirometry, daily asthma symptoms, morning and evening peak expiratory flow and blood parameters were assessed in all, methacholine challenge and inflammatory measures were determined in induced sputum in a subset of patients., Results: Ciclesonide was as effective as prednisolone in improving forced expiratory flow in 1s, morning peak expiratory flow and symptoms, the latter improving more rapidly with ciclesonide. No differences were found in methacholine responsiveness or inflammatory measures in sputum or blood. Ciclesonide caused significantly less reduction in morning plasma cortisol levels (p<0.0001)., Conclusion: This study shows that inhaled ciclesonide (800mug twice daily) has comparable efficacy to oral prednisolone (40mg once daily) to regain asthma control in patients with asthma worsening. The more rapid onset and smaller effect on cortisol suppression suggest a better safety profile of ciclesonide.

Background: Chemical haptens induce both contact and allergic respiratory disease with dendritic cells (DCs) controlling and directing immune responses in vivo. Contact and respiratory haptens may promote differential cytokine production yet distinguishing these effects in vitro remains difficult due to human donor variability. Objective We sought to determine the effect of atopic status on the ability of DC to respond to contact and respiratory sensitizer treatment in vitro as DC from atopic donors are believed to promote Th2-type responses., Methods: Enriched DC from control or atopic donors were treated for 4 h with levels of the contact sensitizer 2,4-dinitrochlorobenzene (DNCB) or the respiratory sensitizer trimellitic anhydride (TMA) that did not reduce cell viability. A sensitive intracellular detection technique was used to measure cytokine production, while T cell responses were assessed in a mixed leucocyte reaction., Results: DC from control, non-atopic, donors produced cytokines differentially in response to sensitizer treatment; DNCB treatment significantly increased the production of Th1 cytokines IL-12 and IFN-gamma while TMA induced the production of IL-13. Control donor DC treated with TMA stimulated less in a mixed leucocyte reaction than untreated cells with any response reduced further by blocking IL-13 in culture. However, DC from atopic donors showed no significant alteration in either cytokine production or T cell stimulatory capacity after sensitizer treatment., Conclusion: Haptens modulate DC by changing the production of cytokines that may play a role in T cell stimulation and subsequent polarization of the immune response. DC from atopic donors were unresponsive to chemical sensitizer treatment, and may be deficient in inducing divergent T cell responses.

Background: Upper airway compromise due to tracheobronchial stenosis commonly occurs in patients with Wegener's granulomatosis (WG). There is at present no consensus on the optimal management of this life threatening condition., Objective: To assess the results of laryngo-tracheo-bronchoscopy, intralesional steroid therapy, laser surgery and dilatation in managing obstructive tracheobronchial WG., Methods: Records of 18 previously untreated stridulous patients with obstructive tracheobronchial WG, treated between 2004 and 2006, were prospectively recorded on an airway database and retrospectively reviewed. Information about patient and lesion characteristics and treatment details were recorded. Treatment progress was illustrated using a timeline plot, and intervention-free intervals were calculated with actuarial analysis., Results: There were nine males and the average age at presentation was 40 (16) years (range 13-74). There were 13 patients with tracheal and five with tracheal and bronchial lesions. The average tracheal lesion height was 8 (3) mm, located 23 (9) mm below the glottis. There were 1, 10 and 7 Myer-Cotton grade I, II and III lesions, respectively. Mean intervention-free interval following minimally invasive treatment was 26 (2.8) months. Following endobronchial therapy, the median intervention-free interval was 22 months (p>0.8 vs tracheal lesions). No patient required a tracheostomy or endoluminal stenting., Conclusions: Intralesional steroid therapy and conservative endoluminal surgery is an effective strategy for treating airway compromise due to active tracheal and bronchial WG, obviating the need for airway bypass or stenting. We recommend the combination of endotracheal dilatation, conservative laser surgery and steroid therapy as the standard of care for treating airway compromise due to obstructive tracheobronchial WG.

Adenosine deaminase (ADA) deficiency is an inherited disorder which leads to elevated cellular levels of deoxyadenosine triphosphate (dATP) and systemic accumulation of its precursor, 2-deoxyadenosine. These metabolites impair lymphocyte function, and inactivate S-adenosylhomocysteine hydrolase (SAHH) respectively, leading to severe immunodeficiency. Enzyme replacement therapy with polyethylene glycol-conjugated ADA is available, but its efficacy is reduced by anti-ADA neutralising antibody formation. We report here carrier erythrocyte encapsulated native ADA therapy in an adult-type ADA deficient patient. Encapsulated enzyme is protected from antigenic responses and therapeutic activities are sustained. ADA-loaded autologous carrier erythrocytes were prepared using a hypo-osmotic dialysis procedure. Over a 9-yr period 225 treatment cycles were administered at 2-3 weekly intervals. Therapeutic efficacy was determined by monitoring immunological and metabolic parameters. After 9 yr of therapy, erythrocyte dATP concentration ranged between 24 and 44 micromol/L (diagnosis, 234) and SAHH activity between 1.69 and 2.29 nmol/h/mg haemoglobin (diagnosis, 0.34). Erythrocyte ADA activities were above the reference range of 40-100 nmol/h/mg haemoglobin (0 at diagnosis). Initial increases in absolute lymphocyte counts were not sustained; however, despite subnormal circulating CD20(+) cell numbers, serum immunoglobulin levels were normal. The patient tolerated the treatment well. The frequency of respiratory problems was reduced and the decline in the forced expiratory volume in 1 s and vital capacity reduced compared with the 4 yr preceding carrier erythrocyte therapy. Carrier erythrocyte-ADA therapy in an adult patient with ADA deficiency was shown to be metabolically and clinically effective.

Objective: chronic obstructive pulmonary disease (COPD) prevalence steadily increases with age. However, the effectiveness of inhaled therapy in the elderly COPD population has rarely been formally evaluated. We studied a group of elderly patients with COPD with a range of severity, selected from one General Practice register to measure peak inspiratory flow (PIF) and assess patient perceived benefit., Methods: we recruited 53 randomly selected elderly patients with COPD (36 males) with a mean age of 73.5 years (range 65-89 years). The evaluation consisted of (i) information obtained from directed questions and (ii) objective measurements of the ability to generate adequate PIF for a variety of inhalers. Patients answered questions regarding ease of use, perceived benefit from and specific problems encountered with their inhaler. Three recordings of PIF were measured at varying inhaled resistances using the 'In-Check Dial'., Results: thirty-five were classified as mild, 17 moderate and 1 severe COPD. All patients used a metered dose inhaler (pMDI), and 12 of the patients also used a dry powder inhaler (DPI). Forty six per cent of patients using a pMDI and 17% of those using a DPI rated their device difficult to use. No patient used a nebuliser. Thirty-one of the 53 patients using just a pMDI felt they were able to perceive benefit in comparison to 4 of the 12 DPI users. Even though most DPI users (10/12) had rated their inhaler as easy to use, 50% were 'unsure' as to whether they received any clinical benefit. Most patients were unable to generate sufficient inspiratory flow to use the higher resistance DPI's and patients with COPD who were able to generate adequate PIF were invariably mild. A significant negative correlation was found between age and the PIF achieved when assessed using the high resistance device setting (R = 0.84, P<0.0001). Multivariate analysis showed the effect of age on PIF was independent of the disease grade., Conclusions: elderly patients with COPD, even when in a stable clinical condition, may be unable to gain optimum benefit from their inhaler.

Background: Dendritic cells (DC) mediate inflammation in rodent models of allergic airway disease, but the role played by human respiratory-tract DC (hRTDC) in atopic asthma remains poorly defined. Recent data suggest that CD1 antigen presentation by hRTDC may contribute to asthma pathogenesis., Objective: To investigate the influence of hRTDC on the balance between atopy and allergic asthma in human subjects and to determine whether CD1 expression by hRTDC is modulated during asthmatic inflammation., Methods: Sputum cells were induced from steroid-naïve, allergen-challenged and allergen-naïve subjects (atopic asthmatics, atopic non-asthmatics and non-atopic controls). hRTDC were identified using monoclonal antibody labelling and analysis by flow cytometry., Results: hRTDC stained HLA-DR(+) (negative for markers of other cell lineages) were predominantly myeloid and comprised approximately 0.5% of viable sputum cells. Sputum cells were potent stimulators of allogeneic CD4(+) naïve T cells and enrichment/depletion experiments correlated stimulatory potency with DC numbers. Sputum contained cells that exhibited typical dendritic morphology when analysed by electron microscopy. Myeloid hRTDC were endocytically active, but uptake of FITC-dextran was enhanced in cells from asthmatics (P<0.001). Despite their increased endocytic capacity, asthmatic myeloid hRTDC appeared mature and expressed increased levels of maturation markers (P<0.05-P<0.001), CD1c, CD1d and langerin (P<0.05). CD1c expression by asthmatic myeloid hRTDC was enhanced upon in vivo allergen challenge (three to ninefold within 24 h; P<0.05). CD11c(-)CD123(high) hRTDC were only detected in asthmatic sputum and were increased in number following allergen challenge., Conclusion: Despite limited cell numbers, it proved possible to analyse human RTDC in induced sputum, providing evidence that increased antigen uptake and enhanced CD1 presentation by activated hRTDC may contribute to allergic airway disease. CD1 presentation by hRTDC in atopic asthma may therefore constitute a novel target for future intervention strategies.

Background: Asthma is a clinical syndrome characterised by chronic inflammation of the lower respiratory tract in which many cells and cellular elements play a role, in particular mast cells, eosinophils, T-lymphocytes, macrophages, neutrophils and epithelial cells. Patients often require long-term anti-inflammatory and reliever drugs to achieve a normal life. This review aims to highlight role of concurrent therapy in the optimal management of asthma., Method: A review of relevant literature was conducted using available medical journals and Science direct via the Internet. The key words employed were: asthma, concurrent therapy, long acting beta agonists and corticosteroids. British Thoracic Society and The National Heart, Lung and Blood Institute websites were also used in sourcing information for this review., Results: Several studies support adding long acting beta agonists (LABA) to inhaled corticosteroids (ICS) than doubling the dose of ICS. This improves lung function, symptoms control and allows the dose of each drug to be adjusted to the patients'needs., Conclusion: This review was able to show that concurrent use LABA and ICS in asthmatics helps in adjusting their treatment within limits hence achieving control of the condition with minimal side effects.

Background: Concomitant methotrexate (MTX) therapy of oral corticosteroid (CS)-dependent asthmatics has been shown to spare CS therapy, but the mechanism is unknown. In a previous report, we showed that MTX increases T cell inhibition by CS. In this report we focus on effects of MTX on immunoglobulin concentrations and their possible clinical relevance., Objective: To monitor changes in circulating leucocytes and Ig in a group of these patients during MTX therapy, and to relate these changes to clinical 'response' as defined by oral CS reduction., Methods: Sixteen severe asthmatics dependent on oral prednisolone 15 (7.5-25) mg/day in addition to high dose inhaled CS were treated with MTX 15 mg intramuscularly, weekly for 28 weeks. Prednisolone dosages were maintained constant for 12 weeks then reduced systematically over the next 16 weeks provided that asthma control did not deteriorate. Patients were classified a priori as 'responders' or 'non-responders' to MTX (reduction of initial oral prednisolone requirement by >or=50% or <50%, respectively). Patients were followed-up for a further 12 weeks after MTX withdrawal. Serum Ig and differential blood leucocyte counts were measured at baseline, 12, 28 and 40 weeks., Results: MTX therapy allowed significant, but individually variable, reductions in oral prednisolone dosages (P<0.00001) without alteration of lung function or symptoms. This was associated with significant reductions in mean serum concentrations of Ig of all classes, which reversed following MTX withdrawal. Reductions in IgE and IgG were significantly greater in the MTX 'responders' as compared with 'non-responders', and changes in IgE, IgG and IgM correlated with changes in prednisolone requirements. Differential blood leucocyte counts showed no significant variation., Conclusion: MTX therapy reduced oral CS requirements in these severe asthmatics to a degree which correlated with reduced circulating Ig but not lymphopaenia, suggesting a possible cause and effect relationship. These reductions might also contribute to the documented incidence of opportunistic infection in these circumstances.

Objective: The aim of this study was to determine the incidence and etiology of pulmonary artery pseudoaneurysms in patients undergoing bronchial angiography for massive hemoptysis and to assess patient outcome after the embolization of these pseudoaneurysms., Conclusion: Peripheral pulmonary artery pseudoaneurysms occur in up to 11% of patients undergoing bronchial angiography for hemoptysis. These are often most easily appreciated on bronchial and/or nonbronchial systemic arterial angiograms because of complete reversal of flow in pulmonary artery branches in the diseased lung. Embolization of bronchial and nonbronchial systemic arteries alone may not be sufficient therapy to control hemoptysis, and occlusion of the pseudoaneurysm itself via a pulmonary artery approach is recommended.

Patient-guided management of asthma using adjustable dosing of budesonide/formoterol in a single inhaler (Symbicort) was compared with fixed dosing in an open-label, multicentre, randomised study. Patients, uncontrolled on an inhaled corticosteroid (ICS) or controlled on an ICS and a long-acting beta2-agonist, entered a 4-week run-in period and received budesonide/formoterol (80/4.5 or 160/4.5 microg), 2 inhalations b.i.d. Following randomisation, the fixed-dosing group (n = 764) continued this regimen for a further 12 weeks. The adjustable-dosing group (n = 775) could step down to 1 inhalation b.i.d. if symptoms were controlled, and, at early signs of worsening symptoms, promptly step up to 4 inhalations b.i.d. for < or = 2 weeks. During run-in, National Heart, Lung and Blood Institute symptom-severity grading was maintained in 60% and improved in 31% of patients, clinic peak flow increased from 400 to 4191/min (P<0.001), and health-related quality of life (overall MiniAQLQ) improved from 4.6 to 5.4 (P<0.001). Patients effectively used the adjustable-dosing regimen; 79% reduced budesonide/formoterol dosage and, compared with fixed dosing, the number of inhalations were significantly lowered (3.2 vs. 3.8 inhalations/day, P<0.05). Both regimens were well tolerated. In both groups, symptom control was maintained or improved in 85-86% of patients, and 94% experienced no treatment failures. Consistent with current guidelines, adjustable maintenance dosing with budesonide/formoterol in a single inhaler provides effective asthma control at reduced medication doses.