A randomised controlled trial of intrapleural balloon intercostal chest drains to prevent drain displacement.

BACKGROUND: Chest drain displacement is a common clinical problem that occurs in 9-42% of cases and results in treatment failure or additional pleural procedures conferring unnecessary risk. A novel chest drain with an integrated intrapleural balloon may reduce the risk of displacement. METHODS: A prospective randomised controlled trial comparing the balloon drain to standard care (12 F chest drain with no balloon) with the primary outcome of objectively defined unintentional or accidental chest drain displacement. RESULTS: 267 patients were randomised (primary outcome data available in 257, 96.2%). Displacement occurred less frequently using the balloon drain (displacement 5 of 128, 3.9%; standard care displacement 13 of 129, 10.1%) but this was not statistically significant (OR for drain displacement 0.36, 95% CI 0.13-1.0, Chi-squared 1 degree of freedom (df)=2.87, p=0.09). Adjusted analysis to account for minimisation factors and use of drain sutures demonstrated balloon drains were independently associated with reduced drain fall-out rate (adjusted OR 0.27, 95% CI 0.08-0.87, p=0.028). Adverse events were higher in the balloon arm than the standard care arm (balloon drain 59 of 131, 45.0%; standard care 18 of 132, 13.6%; Chi-squared 1 df=31.3, p<0.0001). CONCLUSION: Balloon drains reduce displacement compared with standard drains independent of the use of sutures but are associated with increased adverse events specifically during drain removal. The potential benefits of the novel drain should be weighed against the risks, but may be considered in practices where sutures are not routinely used.

Burden of nosocomial COVID-19 in Wales: results from a multicentre retrospective observational study of 2508 hospitalised adults.

The burden of nosocomial SARS-CoV-2 infection remains poorly defined. We report on the outcomes of 2508 adults with molecularly-confirmed SARS-CoV-2 admitted across 18 major hospitals, representing over 60% of those hospitalised across Wales between 1 March and 1 July 2020. Inpatient mortality for nosocomial infection ranged from 38% to 42%, consistently higher than participants with community-acquired infection (31%-35%) across a range of case definitions. Those with hospital-acquired infection were older and frailer than those infected within the community. Nosocomial diagnosis occurred a median of 30 days following admission (IQR 21-63), suggesting a window for prophylactic or postexposure interventions, alongside enhanced infection control measures.

How do you diagnose asthma? A multiple case study design to understand and explain current use of national guidelines by primary care clinicians.

BACKGROUND: Clinical guidelines for asthma are available to UK clinicians but implementation is not straightforward. Diagnostic and treatment inadequacy contribute to patient morbidity and mortality and lack of adherence to guidelines is a component of this. AIM: This qualitative study sought to explore and understand the use of asthma guidelines by primary care clinicians in two geographically bounded regions of Wales. METHOD: Multiple case study design was used. Data was collected using semi-structured interviews with a purposively sampled group of clinical staff from GP practices. Interview transcripts were thematically analysed to produce a detailed picture of practice. RESULTS: Asthma care in the studied areas operated as a social network of clinicians who often used guidelines as boundary objects. Practice and local service design was influenced and dependent on regular input from local secondary care providers. Clinicians looked to British Thoracic Society and Scottish Intercollegiate Guideline Network (BTS/SIGN) 2016 guidelines. There was limited use of National Institute for Health and Care Excellence (NICE) 2017 guidelines. Barriers to guideline recommended diagnostic asthma care included: lack of acceptability, financial costs and disempowerment of nursing staff. CONCLUSION: The findings from this study replicate and reinforce the findings of previous work. It is striking and concerning that the thematic outcomes of this study bear a strong resemblance to that which was demonstrated over a decade ago. The guideline-implementation gap in asthma diagnostics will likely persist unless there is significant restructuring, financial investment and greater empowerment of nursing staff in primary care.

Effect of Thoracoscopic Talc Poudrage vs Talc Slurry via Chest Tube on Pleurodesis Failure Rate Among Patients With Malignant Pleural Effusions: A Randomized Clinical Trial.

Importance: Malignant pleural effusion (MPE) is challenging to manage. Talc pleurodesis is a common and effective treatment. There are no reliable data, however, regarding the optimal method for talc delivery, leading to differences in practice and recommendations. Objective: To test the hypothesis that administration of talc poudrage during thoracoscopy with local anesthesia is more effective than talc slurry delivered via chest tube in successfully inducing pleurodesis. Design, Setting, and Participants: Open-label, randomized clinical trial conducted at 17 UK hospitals. A total of 330 participants were enrolled from August 2012 to April 2018 and followed up until October 2018. Patients were eligible if they were older than 18 years, had a confirmed diagnosis of MPE, and could undergo thoracoscopy with local anesthesia. Patients were excluded if they required a thoracoscopy for diagnostic purposes or had evidence of nonexpandable lung. Interventions: Patients randomized to the talc poudrage group (n = 166) received 4 g of talc poudrage during thoracoscopy while under moderate sedation, while patients randomized to the control group (n = 164) underwent bedside chest tube insertion with local anesthesia followed by administration of 4 g of sterile talc slurry. Main Outcomes and Measures: The primary outcome was pleurodesis failure up to 90 days after randomization. Secondary outcomes included pleurodesis failure at 30 and 180 days; time to pleurodesis failure; number of nights spent in the hospital over 90 days; patient-reported thoracic pain and dyspnea at 7, 30, 90, and 180 days; health-related quality of life at 30, 90, and 180 days; all-cause mortality; and percentage of opacification on chest radiograph at drain removal and at 30, 90, and 180 days. Results: Among 330 patients who were randomized (mean age, 68 years; 181 [55%] women), 320 (97%) were included in the primary outcome analysis. At 90 days, the pleurodesis failure rate was 36 of 161 patients (22%) in the talc poudrage group and 38 of 159 (24%) in the talc slurry group (adjusted odds ratio, 0.91 [95% CI, 0.54-1.55]; P = .74; difference, -1.8% [95% CI, -10.7% to 7.2%]). No statistically significant differences were noted in any of the 24 prespecified secondary outcomes. Conclusions and Relevance: Among patients with malignant pleural effusion, thoracoscopic talc poudrage, compared with talc slurry delivered via chest tube, resulted in no significant difference in the rate of pleurodesis failure at 90 days. However, the study may have been underpowered to detect small but potentially important differences. Trial Registration: ISRCTN Identifier: ISRCTN47845793.

Paraneoplastic phenomenon in mesothelioma.

A 71-year-old man presented with breathlessness and visual disturbance. On examination of the chest, he had signs suggestive of a right-sided pleural effusion and a neurological examination yielded conjugate vertical gaze palsy. Subsequent investigations revealed pleural thickening and mesothelioma. His anti-Ma2 antibodies were positive indicating a paraneoplastic syndrome as the cause of the vertical gaze palsy.

The case for a worldwide ban on smoking in public places.

PURPOSE OF REVIEW: Second-hand smoke (SHS) is a major cause of morbidity and mortality on a global scale. Governments have increasingly sought to mitigate the effects of SHS by introducing legislation that restricts tobacco consumption in public places. There is emerging evidence that such legislation leads to direct and indirect health benefits. RECENT FINDINGS: Exposure to SHS is now shown to be associated with development of cardiovascular disease, and poorer health outcomes in patients with established chronic obstructive pulmonary disease. Childhood (including in-utero) exposure to SHS has recently been linked with increased risk of cleft palate, demonstrable signs of atherosclerosis, and the development of emphysema and lung cancer in adulthood. Comprehensive bans on smoking in public lead to a reduction in overall exposure to SHS for both adults and children and have also been shown to immediately attenuate the incidence of myocardial infarction and paediatric hospital attendances with acute asthma. SUMMARY: Banning smoking in public places is an effective tool for reducing tobacco-related morbidity across a multiplicity of diseases. Countries that have not already done so should introduce legislation to enforce effective legislation that prohibits smoking in public places.

Assessment of small-airways disease using alveolar nitric oxide and impulse oscillometry in asthma and COPD.

The contribution of the alveolar compartment to exhaled nitric oxide (alveolar nitric oxide or CA(NO)) can be calculated as a surrogate of distal inflammation. This value should be corrected for nitric oxide produced in the conducting airways which "back-diffuses" into the alveolar compartment (Corrected CA(NO)). Impulse oscillometry (IOS) (Nava et al., Am J Respir Crit Care Med 168:1432-1437, 2003) is used to derive values for peripheral airways resistance. Twenty-four healthy volunteers, 21 severe asthmatics, 15 mild-to-moderate asthmatics, and 24 COPD patients were assessed with spirometry, impulse oscillometry, and fractionated exhaled nitric oxide. Compared to healthy volunteers, FE(NO) was higher in mild-to-moderate and severe asthmatics: geometric mean fold ratios of 1.91 (P = 0.02) and 2.74 (P < 0.001), respectively. However, there was no difference for mild-to-moderate versus severe asthma. Ratios for CA(NO) were not different for severe asthma versus COPD, but both were elevated compared to that of healthy volunteers [2.64 (P < 0.001) and 3.07 (P < 0.001), respectively] and mild-to-moderate asthma [1.95 (P = 0.04) and 2.28 (P < 0.01)]. However, after correction for axial diffusion, Corrected CA(NO) was increased in COPD compared to severe asthma (geometric mean fold ratio 1.28, P = 0.04), mild-to-moderate asthma (1.34, P < 0.01), and healthy volunteers (1.28, P = 0.02), and there was no difference between other groups. R5 and RF were reduced in healthy volunteers versus mild-to-moderate asthma (P = 0.011 and P < 0.001 respectively), severe asthma (P = 0.002 and P < 0.001), and COPD (P < 0.001 and P < 0.001). Peripheral resistance (R5-R20) was not different for healthy versus mild-to-moderate asthma but was higher in severe asthma (P < 0.001) and COPD (P < 0.001). Correlations were observed between R5-R20 versus FEF(25-75) (r = 0.71, P < 0.01), CA(NO) (r = 0.44, P < 0.01), and Corrected CA(NO) (r = 0.24, P < 0.01). CA(NO) and IOS provide additional information to traditional measures of spirometry and tidal nitric oxide. Previous data reporting elevated alveolar nitric oxide in severe asthma may reflect back-diffusion of nitric oxide from the conducting airways into the alveolar compartment. Corrected CA(NO) and IOS may prove to be useful noninvasive measurements of small-airways disease.

A novel breath-actuated integrated vortex spacer device increases relative lung bioavailability of fluticasone/salmeterol in combination.

BACKGROUND: Spacer devices facilitate respirable drug delivery. A novel breath-actuated antistatic spacer with integrated vortex chamber (Synchro-Breathe) device has been developed, which is compact,portable and user friendly as compared to conventional spacers which are bulky and cumbersome. The relative bioavailability to the lung of inhaled fluticasone and salmeterol combination is primarily dependent on respirable dose delivery and can be reliably quantified using adrenal suppression and early fall in serum potassium (marker of systemic beta-2 adrenoreceptor response) as surrogate markers for delivered lung dose. AIMS AND OBJECTIVES: To compare the in vivo relative bioavailability to the lung of Hydrofluoroalkane(HFA) Seretide delivered via Synchro-Breathe (SB); an optimally prepared 750 ml large volume plastic spacer, Volumatic (VM); and conventional Evohaler pMDI (EH). METHODS: Nineteen healthy volunteers completed the study using a randomised double blind, double dummy crossover design. Single doses of placebo or Seretide HFA 250 (total dose ex-valve: fluticasone 2000 mcg/salmeterol 200 mcg) were administered via SB, VM and EH. Overnight urinary cortisol creatinine (OUCC) and serum potassium (K) were measured at baseline and after each dose as systemic surrogates of relative respirable dose delivery for the fluticasone and salmeterol moieties, respectively. RESULTS: Significant suppression of OUCC and K occurred from baseline with SB and VM but not EH devices(geometric mean fold suppression, 95% CI, p and arithmetic mean fall mmol/L, 95% CI, respectively); EH:1.51(0.43-1.01), p 1/4 0.06; VM: 2.52(1.57-4.04), p < 0.001; SB: 2.66(1.57-4.49), p < 0.001(equating to 33.8%,60.2% and 62.3% falls, respectively). For K, the falls for EH were 0.09(0.25 to 0.07), p 1/4 0.69; VM: 0.27(0.46 to 0.08), p 1/4 0.003; SB: 0.32(0.53 to 0.11), p 1/4 0.002 (equating to 2.2%, 6.8%, and 8.06% fall,respectively). There were no significant differences between SB and VM. CONCLUSION: The breath-actuated Synchro-Breathe device was comparable to an optimally prepared Volumatic spacer, and resulted in commensurate improvement in relative lung bioavailability for both fluticasone and salmeterol moieties compared to pMDI.

A proof-of-concept study to evaluate the antiinflammatory effects of a novel soluble cyclodextrin formulation of nebulized budesonide in patients with mild to moderate asthma.

BACKGROUND: A cyclodextrin solution formulation of budesonide has been developed. OBJECTIVE: To assess the anti-inflammatory effect of a novel soluble formulation of nebulized budesonide compared with the present suspension formulation based on a 1:4 nominal dose ratio. METHODS: Seventeen mild to moderate asthmatic patients were randomized to receive 120 microg of Capsitol-Enabled Budesonide Inhalation Solution (CBIS) twice daily or 500 microg of budesonide suspension (Pulmicort Respules) twice daily via nebulizer for 2 weeks in a crossover manner. Methacholine challenge, fractionated exhaled nitric oxide (NO) measurement, spirometry, and 10-hour overnight urinary creatinine-corrected cortisol measurement were conducted at baseline and after each treatment. RESULTS: Neither CBIS nor Pulmicort significantly improved the provocation concentration of methacholine that caused a decrease in FEV1 of 10% as change from baseline (doubling dilution changes, 0.82; 95% confidence interval [CI], -0.08 to 1.72; P = .08; and 0.86; 95% CI, -0.61 to 2.32; P = .41, respectively). Both CBIS and Pulmicort suppressed exhaled NO from baseline (geometric mean fold ratios: for tidal NO, 0.70; 95% CI, 0.55-0.90; P = .006; and 0.62; 95% CI, 0.50-0.76; P < .001, respectively; for bronchial flux, 0.73; 95% CI, 0.56-0.95; P = .02; and 0.54; 95% CI, 0.39-0.74; P < .001, respectively). Alveolar NO was significantly suppressed by CBIS (geometric mean fold ratio, 0.33; 95% CI, 0.13-0.85; P = .02) but not by Pulmicort (0.66; 95% CI, 0.25-1.76; P = .81). The mean (SEM) nebulization time for CBIS was 84 (3.0) seconds and for Pulmicort was 303 (19) seconds (P < .001). There were no differences between CBIS and Pulmicort for any other outcome. CONCLUSIONS: There are no significant differences between formulations for any inflammatory outcome. CBIS has a shorter nebulization time and is given at a quarter of the nominal dose of Pulmicort.

In vivo comparison of the relative systemic bioavailability of fluticasone propionate from three anti-static spacers and a metered dose inhaler.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: Conventional spacers help overcome problems with co-ordination and may improve lung deposition and decrease oropharyngeal impaction. Antistatic spacers eliminate electrostatic charge and may hence improve respirable dose delivery. The systemic bioavailability of inhaled fluticasone propionate is primarily dependent on delivery by the pulmonary route and hence the performance of antistatic spacers can be evaluated using adrenal suppression as a sensitive surrogate for relative bioavailability to the lung after an inhalation. WHAT THIS STUDY ADDS: This study compares the relative bioavailability to the lung of inhaled fluticasone delivered via conventional pressurized metered dose inhalers (pMDI) and three antistatic spacers (plastic Zerostat-V, plastic Aerochamber Max, and metal Nebuchamber) in patients with asthma. All three antistatic spacers when compared with pMDI significantly increased the relative bioavailability to the lungs of inhaled fluticasone in terms of relative adrenal suppression, and there were no significant differences between the plastic and metal antistatic spacers. AIMS: The systemic bioavailability of inhaled fluticasone propionate (FP) depends primarily on lung absorption and can be quantified by measuring suppression of overnight and early morning urinary cortisol/creatinine (OUCC and EMUCC, respectively). The aim of the study was to determine the relative bioavailability of hydrofluoroalkane (HFA) FP to the lungs via anti-static plastic (Zerostat-V and Aerochamber Max), metal (Nebuchamber) anti-static spacers and metered dose inhaler [Flixotide Evohaler (EH) (pMDI)]. METHODS: A randomized, double-blind, double-dummy, four-way crossover design was used. Eighteen mild to moderate asthmatics received single doses of placebo/HFA-FP 2 mg via the 280-ml Zerostat-V (ZS); 250-ml Nebuchamber (NC); 197-ml Aerochamber Max (AC); and pMDI (EH). Measurements of OUCC and EMUCC were made at baseline and 10 h after each dose. RESULTS: Significant suppression of OUCC and EMUCC occurred from baseline with all three spacers, but not Evohaler (geometric mean fold suppression, 95% confidence interval): ZS, 2.74 (1.75, 4.30), P < 0.001; NC, 3.31 (1.81, 6.06), P < 0.001; AC, 4.98 (3.39, 7.31), P < 0.001; and for EH this was 1.42 (0.92, 2.21), P= 0.169 (equating to a 64, 70, 80 and 30% fall in OUCC via the ZS, NC, AC and EH devices, respectively). There were significant differences between all three spacers vs. EH. When compared with the Evohaler, the Zerostat V resulted in 48% greater suppression (P= 0.009); the Nebuchamber 57% greater suppression (P= 0.001); and the Aerochamber Max 71% greater suppression of OUCC (P < 0.001). CONCLUSION: All three antistatic spacers significantly increased the relative systemic bioavailability of HFA-FP compared with the standard pMDI. --EudraCT Database trial registration number: 2005-005557-22.

Symptoms, spirometry, exhaled nitric oxide, and asthma exacerbations in clinical practice.

BACKGROUND: Patient symptoms, spirometry measurements, exacerbation rates, and exhaled nitric oxide (FE(NO)) levels have all been used to quantify asthma severity. OBJECTIVE: To determine the relationships among these disease surrogates in clinical practice. METHODS: Data were collected from 5 primary care asthma clinics on patient symptoms, reliever use, spirometry measurements, maintenance pharmacotherapy, disease severity (British Thoracic Society treatment step), and FE(NO) level. Exacerbation data (asthma-related unscheduled health care contact or rescue oral corticosteroid therapy) for the 12 months before and 3 months after the clinic visit were then obtained. RESULTS: A total of 267 adult asthmatic patients (mean [SEM] age, 51.6 [1.1] years; forced expiratory volume in 1 second, 86.3% [1.2%] of predicted) participated, and 157 exacerbations were captured. For the 12 months before the clinic visit, exacerbation rate was positively correlated with dose of inhaled corticosteroid (P < .001), treatment step (P < .001), reliever use (P = .002), and symptom score (P < .001) but was negatively correlated with FE(NO) level (P = .04); only symptom scores correlated with exacerbation rate in the 3 months after the visit. Levels of FE(NO) were significantly lower in frequently exacerbating patients receiving higher doses of maintenance inhaled corticosteroids compared with patients with mild disease who were corticosteroid naive (19.7 vs 40.4 ppb, P < .001). Measurement of FE(NO) was an insensitive method (sensitivity, 66.7%; specificity, 51.9% at a cutoff value of 20 ppb) for identifying patients who subsequently exacerbated. CONCLUSION: Levels of FE(NO) are paradoxically decreased in patients with more severe asthma and frequent exacerbations and may, therefore, be of limited utility in primary care.

Respirable dose delivery of fluticasone propionate from a small valved holding chamber, a compact breath actuated integrated vortex device and a metered dose inhaler.

AIMS: To compare the respirable dose delivery of the hydrofluroalkane fluticasone propionate (HFA-FP) via an optimally prepared Aerochamber Plus spacer (AP), via a Synchro-Breathe (SB) device, and pMDI Evohaler (EH). METHODS: Seventeen mild to moderate asthmatics completed the study using a randomized, double-blind, double-dummy, three way crossover design. Single doses of placebo or HFA-FP 2.0 mg were administered via the EH, AP, and SB devices. The overnight urinary cortisol : creatinine ratio (OUCC) was measured at baseline and after each dose. RESULTS: Significant suppression of OUCC occurred from baseline with AP and SB but not EH devices (geometric mean fold suppression, 95% CI): AP: 3.18 (2.29, 4.36), P < 0.001; SB: 1.79 (1.31, 2.40), P = 0.001; EH: 1.12 (0.69, 1.44), p = 0.37 (equating to 68%, 45% and 9% falls, respectively). Significant differences in OUCC between devices were as follows: (geometric mean fold difference, 95% CI): AP vs. EH. 2.83 (2.09, 3.82), P < 0.001; AP vs. SB: 1.78 fold (1.21, 2.60), P = 0.003; SB vs. EH: 1.59 (1.09, 2.31), P = 0.013 (equating to 65%, 44% and 37% differences, respectively). CONCLUSIONS: The use of an optimally prepared AP spacer and breath actuated SB device, when compared with pMDI, significantly increased the respirable dose of HFA-FP.

Effect of aspirin on airway inflammation and pulmonary function in patients with persistent asthma.

BACKGROUND: Aspirin can cause bronchoconstriction in some asthmatic patients through increased production of proinflammatory mediators, particularly leukotrienes. However, recent in vivo evidence has suggested that aspirin also triggers the production of lipoxins, which act as natural antagonists of prostaglandins and leukotrienes. Aside from patients with known aspirin-sensitive asthma, physicians have avoided the use of aspirin in asthmatic patients in general because it was believed that this agent might precipitate worsening of their condition. OBJECTIVE: We sought to establish the effect of aspirin on pulmonary inflammation and function in patients with persistent asthma. METHODS: After withdrawal of their usual anti-inflammatory medication, patients with mild-to-moderate persistent asthma undertook double-blind, randomized, crossover treatment with 75 mg/d aspirin and placebo for 3 weeks each. Treatment evaluation included histamine challenge, spirometry, impulse oscillometry, total and alveolar exhaled nitric oxide measurement, and serum thromboxane B2 and 15-epilipoxin A4 levels. RESULTS: Fifteen patients completed the trial. Compared with placebo, there were no differences in histamine PC(20) values (0.17 doubling-dilution shift; 95% CI, -0.38 to 0.73; P = 1), exhaled nitric oxide levels (0.95-fold change; 95% CI, 0.45-2.00; P = 1), or any other inflammatory, spirometric, or oscillometry measurements. Aspirin led to a significant decrease in thromboxane B2 levels (17.53-fold difference; 95% CI, 5.46-56.49; P < .001). Baseline 15-epilipoxin A4 levels were increased at 4.88 ng/mL, and there was no increase with aspirin versus placebo (0.99-fold difference; 95% CI, 0.79-1.24; P = 1). CONCLUSION: In this preliminary study of 15 patients, low-dose aspirin did not lead to increased 15-epilipoxin A4 synthesis or alter inflammatory markers in patients with mild-to-moderate persistent asthma.

An in vivo and in vitro comparison of inhaled steroid delivery via a novel vortex actuator and a conventional valved holding chamber.

BACKGROUND: Valved holding chambers improve delivery of inhaled corticosteroids to the lung but are bulky in design. A novel compact vortex actuator device has therefore been developed. OBJECTIVES: To compare the in vitro and in vivo performance of a novel compact vortex actuator (the Neohaler [NH]) vs a conventional small-volume valve holding chamber (the AeroChamber Plus [AP]. METHODS: Seventeen asthmatic patients completed the study per protocol, receiving 4 weeks each of 100 microg/d (50-microg formulation) or 400 microg/d (100-microg formulation) of hydrofluoroalkane beclomethasone dipropionate via the NH or AP devices in a randomized crossover, double-blind, double-dummy, placebo-controlled design. The doubling dilution (dd) shift in methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (primary outcome) was used to evaluate anti-inflammatory effects and adrenal function to measure systemic exposure. The fine particle (<4.7 tm) dose was evaluated using an Andersen Cascade Impactor. RESULTS: A total of 100 microg of hydrofluoroalkane beclomethasone dipropionate via the NH and AP produced 0.95-dd (95% confidence interval [CI], 0.44-1.45; P = .006) and 0.45-dd (95% CI, -0.16 to 1.06; P = .83) improvements from baseline in methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20%, respectively, with no statistically significant difference between devices: 0.50 dd (95% CI, -0.25 to 1.24; P = .18). At 400 microg/d, 1.08-dd (95% CI, 0.49-1.67; P = .006) and 0.85-dd (95% CI, 0.32-1.39; P = .02) improvements were found for the NH and AP, respectively, with a 0.23-dd difference (95% CI, -0.28 to 0.74; P = .36) between devices. No adrenal suppression occurred with either device. The in vitro fine particle dose was 39.1 microg for the NH and 39.0 microg for the AP with the 100-microg formulation and 26.0 g and 25.2 microg, respectively, with the 50-microg formulation. CONCLUSIONS: Delivering hydrofluoroalkane beclomethasone dipropionate via the NH and AP attenuates asthmatic airway inflammation to a comparable degree and produces a similar in vitro fine particle dose profile.

Portable exhaled nitric oxide measurement: Comparison with the "gold standard" technique.

BACKGROUND: The measurement of fractional exhaled nitric oxide (FENO) can assist in the diagnosis of asthma and may also act as a useful surrogate inflammatory marker on which to base treatment decisions in asthma management algorithms. Until recently, this technique was confined to research facilities and secondary care institutions. A portable nitric oxide analyzer (MINO; Aerocrine AB; Smidesvägen, Sweden) has been developed, but few data exist comparing this device with established, larger laboratory-based analyzers (NIOX; Aerocrine AB). METHODS: A total of 101 asthmatic patients (64 treated with regular inhaled corticosteroids) and 50 healthy volunteers had simultaneous FENO measurements undertaken using NIOX and MINO devices. RESULTS: In both asthmatic patients and healthy volunteers, there was a good correlation between the measurements obtained using each device (r = 0.94 and 0.96, respectively). Altman-Bland plots confirmed this agreement. Receiver operating characteristic curves discriminating asthmatic patients from healthy volunteers obtained using the NIOX and MINO showed a sensitivity of 83.2% and a specificity of 72% using cutoff values of 13 and 12.5 parts per billion, respectively. CONCLUSION: FENO values obtained using a portable analyzer correlate well with those obtained using an established laboratory analyzer and can be used to discriminate asthmatic from nonasthmatic patients. This may facilitate the measurement of asthmatic airway inflammation in primary care.

Simvastatin does not exhibit therapeutic anti-inflammatory effects in asthma.

BACKGROUND: Statins lower cholesterol and also exhibit anti-inflammatory properties. In vitro and animal studies have suggested they may be useful for the treatment of a number of inflammatory conditions. OBJECTIVE: To evaluate the in vivo therapeutic potential of simvastatin as an anti-inflammatory agent in patients with asthma. METHODS: Potential signal from treatment effect was optimized by withdrawing all anti-inflammatory treatment for the duration of the study. Participants received 1 month of daily simvastatin and 1 month of daily placebo in a randomized, double-blind crossover trial. A total of 16 patients completed per protocol. Asthmatic inflammation was evaluated by measuring exhaled tidal nitric oxide, alveolar nitric oxide, sputum and peripheral eosinophil count, methacholine hyperresponsiveness, salivary eosinophilic cationic protein, and C-reactive protein. Measurements of dynamic and static lung volumes and of cholesterol were also made. RESULTS: After initial withdrawal of usual asthma medication, there was a 1.43 geometric mean fold increase (ie, 43% difference) in fraction of exhaled nitric oxide (95% CI, 1.15 to 1.78; P = .004). Compared with placebo, simvastatin led to a 0.86 geometric mean fold decrease (95% CI, 0.7 to 1.04; P = .15) in exhaled nitric oxide (ie, a 14% difference), and a -0.18 doubling dilution shift (95% CI, -1.90 to 1.55; P = 1.0) in methacholine hyperresponsiveness. There were no significant differences in other inflammatory outcomes, lung volumes, or airway resistance between simvastatin and placebo. Treatment with simvastatin led to a significant reduction (P < .005) of total and low-density lipoprotein cholesterol. CONCLUSION: There is no evidence to suggest simvastatin has anti-inflammatory activity in patients with asthma. CLINICAL IMPLICATIONS: Simvastatin is not useful for the treatment of asthma.

Respiratory symptoms, pulmonary function, and markers of inflammation among bar workers before and after a legislative ban on smoking in public places.

CONTEXT: Scotland prohibited smoking in confined public places on March 26, 2006. OBJECTIVE: To investigate the association of smoke-free legislation with symptoms, pulmonary function, and markers of inflammation of bar workers. DESIGN, SETTING, AND PARTICIPANTS: This prospective observational study was conducted in Tayside, Scotland from February-June 2006. One hundred five nonasthmatic and asthmatic nonsmoking bar workers were initially enrolled, of whom 77 completed the study per protocol. MAIN OUTCOME MEASURES: Respiratory and sensory symptoms, spirometry measurements, serum cotinine levels, peripheral inflammatory cell count, asthma quality-of-life scores, and exhaled nitric oxide levels were evaluated before and after introduction of the smoking ban. RESULTS: For the per-protocol analysis, the percentage of bar workers with respiratory and sensory symptoms decreased from 79.2% (n = 61) before the smoke-free policy to 53.2% (n = 41) (total change, -26%; 95% confidence interval [CI], -13.8% to -38.1%; P<.001) and 46.8% (n = 38) (-32.5%; 95% CI, -19.8% to -45.2%; P<.001) 1 and 2 months afterward. Forced expiratory volume in the first second increased from 96.6% predicted to 104.8% (change, 8.2%; 95% CI, 3.9% to 12.4%; P<.001) and then 101.7% (change, 5.1%; 95% CI, 2.1% to 8.0%; P = .002), and serum cotinine levels decreased from 5.15 ng/mL to 3.22 ng/mL (change, -1.93 ng/mL; 95% CI, -2.83 to -1.03 ng/mL; P<.001) and then 2.93 ng/mL (-2.22 ng/mL; 95% CI, -3.10 to -1.34 ng/mL; P<.001). The total white blood cell and neutrophil count was reduced from 7610 to 6980 cells/microL at 2 months (-630 cells/muL; 95% CI, -1010 to -260 cells/microL; P = .002) and from 4440 to 4030 cells/microL (-410 cells/microL; 95% CI, -740 to -90 cells/microL; P = .03), respectively. Asthmatic bar workers also had less airway inflammation, with a reduction in exhaled nitric oxide from 34.3 parts per billion (ppb) to 27.4 ppb 1 month after the ban (0.8-fold change; 95% CI, 0.67 to 0.96 ppb; P = .04), and Juniper quality-of-life scores increased from 80.2 to 87.5 points (7.3 points; 95% CI, 0.1 to 14.6 points; P = .049). CONCLUSIONS: Smoke-free legislation was associated with significant early improvements in symptoms, spirometry measurements, and systemic inflammation of bar workers. Asthmatic bar workers also had reduced airway inflammation and improved quality of life.

Non-invasive measurement of airway inflammation in asthma.

Assessing the severity and control of a patient's asthma is of great importance to ensure that pharmacotherapy is optimized. Measures such as lung function, symptoms, and reliever use have traditionally been used as objective means of undertaking this assessment, but until now the level of airway inflammation has not been quantified. As asthma is primarily an inflammatory disorder, it would be desirable to include a measure of this process when evaluating disease control. The following article outlines methods of non-invasively measuring asthmatic airway inflammation and highlights their potential role in clinical practice.