Daniel Menzies

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; Smidesvagen, 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.

Original Research: AsthmaPortable Exhaled Nitric Oxide Measurement

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; Smidesvagen, 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.

Non-invasive measurement of airway inflammation in asthma.

Assessing the severity and control of a patients 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.

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.

Differential anti-inflammatory effects of large and small particle size inhaled corticosteroids in asthma.

Background:  Extra‐fine particle formulations of hydrofluoroalkane‐134a beclometasone dipropionate (HFA‐BDP) exhibit clinical effects comparable with conventional particle formulations of chlorofluorocarbon beclometasone dipropionate (CFC‐BDP) at half the dose. There is little data comparing their effects on inflammation. We have evaluated the effects of HFA‐BDP and CFC‐BDP on pulmonary and systemic markers of asthmatic inflammation.

A proof-of-concept study to evaluate the anti-inflammatory 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.

Comparison of measured exhaled nitric oxide at varying flow rates

Altered levels of exhaled nitric oxide (FeNO) have been well documented in a number of conditions, although it is in asthma that this phenomenon has been most extensively investigated.1 Raised FeNO levels in patients with asthma have been correlated not only with other markers of airway inflammation (including induced sputum eosinophil count), but also with airway hyperresponsiveness and response to inhaled corticosteroids.2 Furthermore, the detection of a raised FeNO level has been shown to have a positive predictive value of up to 95% for the diagnosis of asthma.3 A number of …

Making Light of an Interstitial Process

A 58-year-old woman with breathlessness was found to have inspiratory crackles on auscultation throughout her thorax. Highresolution computed tomography (Figure 1) demonstrated interlobular septal thickening with ground glass opacities and nodularity. An open lung biopsy (Figure 2) stained using Congo Red and viewed under crossed beams of polarized light revealed the characteristic “apple green” dichroism unique to amyloid as a consequence of its molecular b-pleated sheet configuration. Immunofixation of the serum revealed a faint band at the near-g region, which was subsequently typed as free lambda light chains. Pulmonary parenchymal amyloid is rare, and even more uncommon as an isolated end-organ manifestation of this systemic disease as was the case in our patient (1, 2). Our patient responded well to treatment with bortezomib, cyclophosphamide, and dexamethasone, and remains clinically stable 8 months from initial diagnosis. Clinicians should remain vigilant for systemic conditions manifesting primarily with pulmonary involvement.

A Lung Mass Causing Cardiovascular Impairment

A 58-year-old woman presented to our hospital with progressive breathlessness and cough. Her cough, which had not responded to empiric antibiotic therapy initiated by her family physician, had initially developed 6 weeks previously. Two weeks prior to hospital admission, she noted worsening of the cough and the development of breathlessness, with the result that her usually unlimited exercise tolerance was reduced to approximately 20 yards. Her previous medical, occupational, and travel histories were unremarkable, and she had been receiving no regular medication. She was currently a smoker with a total of 20 pack-years. On examination, the patient was centrally cyanosed with resting oxygen saturations of 78% while breathing room air. Her jugular venous pressure was elevated, and there was moderate peripheral ankle edema that was compatible with right heart failure. An examination of her chest revealed a dull percussion note and reduced breath sounds throughout the right hemithorax. Arterial blood gas analysis performed with the patient breathing 1 L of oxygen via nasal cannula demonstrated the following results, consistent with acute-on-chronic type II respiratory failure: pH, 7.27; Po2, 101.5 mm Hg; Pco2, 82.0 mm Hg, and bicarbonate concentration, 36 mmol/L. Renal and liver function test results were normal, as were hematologic parameters, including a CBC with cell differential. The chest radiograph obtained at hospital admission (Fig 1) identified a large, confluent, welldemarcated mass filling the majority of the right hemithorax, with encroachment toward the mediastinum and associated displacement of the central structures including the heart. Subsequent contrast-enhanced CT scans of the thorax (Fig 2A and B) and abdomen also demonstrated the presence of a large mass that measured approximately 18 16 cm in the axial plane, impinging on and compressing both the inferior vena cava and right atrium. No significant thoracic or extrathoracic adenopathy was identified. The mass appeared to