Bronchodilator delivery by metered-dose inhaler in mechanically ventilated COPD patients: influence of end-inspiratory pause. Terbutaline in COPD comparison between turbuhaler® and chlorofluorocarbon (CFC) inhaler Diagnosing viral and bacterial respiratory infections in acute COPD exacerbations by an electronic nose: a pilot study. What is the optimal treatment strategy for chronic obstructive pulmonary disease exacerbations? Comparison of respiratory parameters and plasma cytokine levels between treatment with Salmeterol/fluticasone and ipratropium/terbutaline/budesonide in mechanically ventilated COPD patients. Aerosol bronchodilator delivery methods. Relative impact on pulmonary function and cost of respiratory care. The course of inhalation profiles during an exacerbation of obstructive lung disease. Bronchodilator therapy with metered-dose inhaler and spacer versus nebulizer in mechanically ventilated patients: comparison of magnitude and duration of response. A randomized study of formoterol fumarate in a porous particle metered-dose inhaler in patients with moderate-to-severe COPD. The relative lung and systemic bioavailability of terbutaline following nebulisation in non-invasively ventilated patients. beta(2)-Agonist delivery via a resuscitator bag (Ambu MediBag): a comparison with a metered-dose inhaler using the Volumatic-Spacer. Teaching time for metered-dose inhalers in the emergency setting. Onset of action following formoterol Turbuhaler and salbutamol pMDI in reversible chronic airway obstruction. Equivalence of continuous flow nebulizer and metered-dose inhaler with reservoir bag for treatment of acute airflow obstruction. Clinical outcomes and treatment cost comparison of levalbuterol versus albuterol in hospitalized adults with chronic obstructive pulmonary disease or asthma. Randomized Controlled Trial of a Breath-Activated Nebulizer in Patients with Exacerbation of COPD Treatment of patients hospitalized for exacerbations of chronic obstructive pulmonary disease: comparison of an oral/metered-dose inhaler regimen and an intravenous/nebulizer regimen. Resource use and risk factors in high-cost exacerbations of COPD. Inhaled fenoterol-ipratropium bromide in mechanically ventilated patients with chronic obstructive pulmonary disease. Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room. Nebulizer vs spacer for bronchodilator delivery in patients hospitalized for acute exacerbations of COPD. Cost-benefit comparison of aerosol bronchodilator delivery methods in hospitalized patients. Nebulized wet aerosol treatment in emergency department--is it essential? Comparison with large spacer device for metered-dose inhaler. A randomized controlled trial to assess the optimal dose and effect of nebulized albuterol in acute exacerbations of COPD. Comparison of a hand-held nebulizer with a metered dose inhaler-spacer combination in acute obstructive pulmonary disease. Studies of ipratropium bromide and fenoterol administered by metered-dose inhaler and aerosolized solution. The effect of indacaterol during an acute exacerbation of COPD.
The delivery of bronchodilators with a metered-dose inhaler ( MDI ) and a spacer in mechanically ventilated patients has become widespread practice . However , the various ventilator setting s that influence the efficacy of MDI are not well established . Application of an end-inspiratory pause ( EIP ) during drug delivery has been suggested as one of the factors that might increase the effectiveness of this therapy . To test this , the effect of EIP on the bronchodilation induced by beta2-agonists administered with MDI and a spacer in a group of mechanically ventilated patients with chronic obstructive pulmonary disease ( COPD ) was examined . Twelve patients with COPD , mechanically ventilated on volume-controlled mode , were prospect ively r and omized to receive six puffs of salbutamol ( 100 microg x puff(-1 ) ) either with or without EIP of 5 s duration . Salbutamol was administered with an MDI adapted to the inspiratory limb of the ventilator circuit using an aerosol cloud-enhancer spacer . After a 6 h wash-out , patients were crossed over to receive salbutamol by the alternative mode of administration . Static and dynamic airway pressures , minimum ( Rmin ) and maximum ( Rmax ) airflow resistance , the difference between Rmax and Rmin ( deltaR ) , static end-inspiratory respiratory system compliance ( Cst , rs ) and cardiac frequency ( fc ) were measured before and at 15 , 30 and 60 min after salbutamol administration . Salbutamol caused a significant decrease in dynamic and static airway pressures , Rmin and Rmax . These changes were not influenced by application of EIP and were evident at 15 , 30 and 60 min after salbutamol . With and without EIP , Cst , rs , deltaR and fc did not change after salbutamol . In conclusion , salbutamol delivered with a metered-dose inhaler and a spacer device induced significant bronchodilation in mechanically ventilated patients with chronic obstructive pulmonary disease , the magnitude of which was not affected by an end-expiratory pause of 5 s. These results do not support the use of end-inspiratory pause when bronchodilators are administered in adequate doses during controlled mechanical ventilation Patients with chronic obstructive pulmonary disease ( COPD ) often subjectively benefit from inhaled R2-agonists in spite of little or no demonstrable effect in forced expiratory volume in 1 second ( FEV1.0 ) . A comparison between the effects of terbutaline administered via a dry powder inhaler ( Turbuhaler ® ) and via a chlorofluorocarbon ( CFC ) inhaler in conjunction with a spacer device ( Nebuhaler ® ) was performed in patients with regard to FEV1.0 , forced expiratory capacity ( FVC ) , residual volume ( RV ) , and specific conductance ( s-Gaw ) . Fifteen hospitalised patients ( 11 male ) with COPD were studied , each of whom had a diurnal variation in peak expiratory flow ( PEF ) not exceeding 15 % and with a demonstrated volume response to inhaled β2-agonists in FVC and /or RV of at least 15 % . Patients were administered each of the following five treatments on a single occasion in a r and omized order ( latin square ) in intervals of at least 2 days : placebo , terbutaline via Turbuhaler ( 1.0 and 2.5 mg ) and terbutaline via a CFC inhaler ( 1.0 mg without and 2.5 mg with Nebuhaler ) . Inhalation of terbutaline in different doses and from different devices induced a decrease in RV , an increase in FVC , and s-Gaw and a less pronounced increase in FEV1.0 . No statistically significant differences between the four terbutaline treatments were seen , but all were significantly different from the placebo . These findings indicate that while patients with COPD may benefit from inhaled terbutaline through decreased hyperinflation , the choice of inhalation device seems to be of little importance for its efficacy Respiratory infections , viral or bacterial , are a common cause of acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) . A rapid , point-of-care , and easy-to-use tool distinguishing viral and bacterial from other causes would be valuable in routine clinical care . An electronic nose ( e-nose ) could fit this profile but has never been tested in this setting before . In a single-center registered trial ( NTR 4601 ) patients admitted with AE COPD were tested with the Aeonose ( ® ) electronic nose , and a diagnosis of viral or bacterial infection was obtained by bacterial culture on sputa and viral PCR on nose swabs . A neural network with leave-10%-out cross-validation was used to assess the e-nose data . Forty three patients were included . In the bacterial infection model , 22 positive cases were tested versus the negatives ; and similarly 18 positive cases were tested in the viral infection model . The Aeonose was able to distinguish between COPD -subjects suffering from a viral infection and COPD patients without infection , showing an area under the curve ( AUC ) of 0.74 . Similarly , for bacterial infections , an AUC of 0.72 was obtained . The Aeonose e-nose yields promising results in ' smelling ' the presence or absence of a viral or bacterial respiratory infection during an acute exacerbation of COPD . Validation of these results using a new and large cohort is required before introduction into clinical practice The present study aims to determine whether treating chronic obstructive pulmonary disease ( COPD ) exacerbations with intravenous steroids and aerosol bronchodilators ( group I ) is superior to oral steroids and multiple dose inhaler ( MDI ) bronchodilators with a spacer ( group II ) . Group I received 40 mg methylprednisolone·day−1 intravenously with a decrease to 20 mg after 10 days and a further decrease of 4 mg·4 days−1 . Aerosol therapy consisted of 10 mg salbutamol and 1 mg ipratropiumbromide·day−1 . Group II received 32 mg methylprednisolone orally for 1 week followed by 24 mg·day−1 for 4 days and a subsequent decrease of 4 mg·week−1 . Duovent ® MDI with a spacer was given at a dose of 1.6 mg fenoterol and 640 µg ipratropiumbromide·day−1 . In group I ( n=19 ) forced expiratory volume in one second ( FEV1 ) rose from 0.82±0.46 to 0.91±0.47 L and average dyspnoea decreased from 6.0±1.9 to 4.1±2.6 within 10 days . The Chronic Respiratory Disease Index Question naire ( CRQ ) score increased from 78±24 to 90±24 points after 4 weeks . In group II (  n=18 ) FEV1 increased from 0.70±0.27 to 0.90±0.29 L , dyspnoea regressed from 6.2±2.4 to 2.7±2.6 and CRQ from 67±17 to 86±20 . Both groups showed similar results in dropout rate , length of hospital stay and patient satisfaction . In conclusion , the two treatment strategies appear equally effective in treating chronic obstructive pulmonary disease exacerbations , although oral steroids and metered dose inhaler bronchodilators appear associated with a higher risk of hospital re-admission BACKGROUND It is unknown whether the bronchodilation and anti-inflammatory effects of inhaled salmeterol and fluticasone ( SF ) are better than those of traditionally inhaled ipratropium , terbutaline and budesonide ( ITB ) in mechanically ventilated patients with chronic obstructive pulmonary disease ( COPD ) . METHODS Nineteen stable COPD patients with respiratory failure were r and omly enrolled into two groups . Patients were treated with inhaled SF delivered by a metered-dose inhaler with a spacer or with inhaled nebulized ITB . Respiratory parameters were measured for 7 days and plasma cytokine levels were measured on days 1 and 7 . RESULTS The kinetic curve of the rapid shallow index ( RSI ) from day 1 to day 7 was significant lower in the SF group than that in the ITB group . There were no significant differences in minute ventilation , intrinsic positive end expiratory pressure , and airway resistance between the ITB and SF groups from day 1 to day 7 . There were no differences in plasma interleukin (IL)-6 , IL-10 , IL- 12 , and transforming growth factor-beta1 levels between day 1 and day 7 in the ITB or SF group . CONCLUSIONS Patients with inhaled SF treatment had a lower RSI . The effects of bronchodilators and anti-inflammation were similar between inhaled SF and ITB in COPD patients with ventilator support Thirty-six acutely III , hospitalized patients with acute exacerbations of obstructive airway disease and a greater than 10 % increase in forced expiratory volume in 1 s after administration of aerosolized bronchodilator were r and omized to receive either metaproterenol sulfate delivered by updraft-compressor nebulization ( UDN ) or terbutaline sulfate delivered by metered-dose inhaler ( MDI ) with a spacer . Serial analyses of pulmonary function measurements were performed with the use of 95 % confidence intervals for the percentage response ratios of MDI to UDN . The response to MDI was at least equivalent to that of UDN , and MDI use was associated with no prolongation of hospital stay . Equivalent bronchodilation was achieved with MDI therapy with a lower daily charge for therapy for each patient and less respiratory therapist time . In hospitalized bronchodilator-responsive patients with acute exacerbations of obstructive airway disease , the MDI/spacer combination is the preferred approach when the status of the patient allows its use BACKGROUND Acute exacerbations of asthma and chronic obstructive pulmonary disease ( COPD ) are associated with increased airflow Limitation , hyperinflation and respiratory muscle fatigue . It is unclear , whether patients are able to perform adequate inhalations through various inhalation devices with different orfices during an exacerbation . The aim of this study was to examine the evolution of inhalation profiles of patients inhaling through Diskus , Turbuhaler , pressurized metered dose inhaler ( pMDI ) and Volumatic and consequently the appropriateness of using the various devices during an exacerbation . MEASUREMENTS 15 hospitalized patients participated in this r and omized comparison of inhalation profiles through the four placebo-devices . For each device , triplicate inhalation profiles were recorded during day 1 - 9 of admission and in stable phase ( day 50 ) . RESULTS The mean percentage of patients performing optimum inhalation profiles was 100 % for Diskus , 60 % for Turbuhaler , 14 % for pMDI and 87 % for Volumatic over the interval of day 1 - 9 and day 50 . Patients with an inspiratory muscle strength ( MIP ) of less than 6kPa were generally unable to generate the optimum flow through the Turbuhaler ( > 60 l/min ) . CONCLUSION The Diskus and Volumatic can be used effectively in the acute phase of an exacerbation of asthma or COPD . The Turbuhaler could be optimally used after the fifth day of convalescence . The pMDI is rather unsuitable during an exacerbation OBJECTIVE Four-hour comparison of the bronchodilator response of albuterol administered via metered-dose inhaler ( MDI ) with spacer versus small-volume nebulizer ( SVN ) to mechanically ventilated patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN Prospect i ve r and omized clinical trial . SETTING Medical intensive care unit in a university hospital . PATIENTS Thirteen mechanically ventilated COPD patients . INTERVENTION Albuterol administration of 4 puffs ( 0.4 mg ) or 10 puffs ( 1.0 mg ) via MDI with spacer or 2.5 mg via SVN to mechanically ventilated patients in order to assess the bronchodilator response over 4 hours . MEASUREMENTS AND RESULTS Mechanically ventilated patients were enrolled in a r and omized crossover study wherein one group received 4 puffs ( 0.4 mg ) or 2.5 mg of albuterol and another group received 10 puffs ( 1.0 mg ) or 2.5 mg of albuterol on separate days . Respiratory mechanics measurements were obtained over 4 hours . Total airway resistance declined by 14.4 + /- 3.8 % after 4 MDI puffs , 18.3 + /- 1.8 % after 10 MDI puffs , or 13.7 + /- 2.6 % after 2.5 mg via SVN , compared to baseline ( p < 0.01 ) . After albuterol delivery , airway resistance remained improved for 90 - 120 minutes ( p < 0.05 ) and returned to baseline by 4 hours with all treatments . CONCLUSION The airway response to albuterol administration via MDI and SVN to mechanically ventilated patients was similar in magnitude and duration , returning to baseline by 240 minutes . In stable , mechanically ventilated COPD patients , albuterol may be administered via MDI with spacer or via SVN every 4 hours BACKGROUND Formoterol fumarate ( FF ) is a well-established long-acting β2-agonist . This represents the first clinical study of FF in a metered-dose inhaler ( FF MDI ) based on proprietary lipid-based porous-particle engineering technology . METHODS In this r and omized , double-blind , 5-period , crossover study ( NCT00880490 ) , subjects received 2.4 , 4.8 , and 9.6 μg of FF MDI , open-label Foradil ( ® ) Aerolizer ( ® ) ( FA ) 12 μg , and placebo .  Spirometry was performed at baseline , 15 and 30 min , and 1 , 2 , 4 , 6 , 8 , 10 , 11.5 , and 12 h post-dose . RESULTS Thirty-four subjects were enrolled .  Improvement in forced expiratory volume in 1 s ( FEV1 ) was similar between FF MDI 9.6 μg and FA . Change in FEV1 area under the curve for 0 - 12 h ( AUC0 - 12 ) for each FF MDI dose demonstrated superior efficacy versus placebo ( P < .001 for all 3 doses ) . Over 12 h and at each time point , FF MDI 9.6 μg was non-inferior to FA for FEV1 AUC0 - 12 with the 95 % CI 's supporting a maximum difference of approximately 45 mL. Peak and trough FEV1 , forced vital capacity , peak expiratory flow rate , peak inspiratory capacity , and pharmacokinetics confirmed the primary endpoint , with dose ordering of the FF MDI 2.4 , 4.8 , and 9.6 μg , and comparability of FF MDI 9.6 μg to FA . All 3 doses of FF MDI were safe and well-tolerated , with a safety profile similar to that of placebo and FA . CONCLUSIONS The efficacy and pharmacokinetic profile of FF MDI 9.6 μg were comparable to FA 12 μg and with similar safety to placebo and FA . TRIAL REGISTRATION This clinical trial was registered on Clinical Trials.gov , Identifier : NCT NCT00880490 Nebulising a bronchodilator during non-invasive ventilation ( NIV ) is effective but there is a lack of consensus on the system to use because comparator in vivo studies in these patients are difficult . Urinary pharmacokinetic methodology post inhalation could provide this information . Chronic obstructive pulmonary disease patients requiring NIV received r and omised study doses of either 2 mg terbutaline nebulised from an Aeroneb Pro ( AERO ) or 5 mg from a Sidestream ( SIDE ) on days 1 and 3 of admission . Urine sample s were provided at 30 min then pooled up to 24h post inhalation and amounts of urinary terbutaline ( UTER0.5 and UTER24 ; indices of relative lung and systemic bioavailability , respectively ) were determined . Twelve consenting patients receiving NIV mean ( SD ) age and weight of 74.8 ( 8.2 ) years and 61.0 (10.7)kg completed the study . The mean ( SD ) UTER0.5 following AERO and SIDE was 9.4 ( 3.7 ) and 10.4 ( 4.1 ) μg with a mean ratio ( 90 % confidence interval ) of 89.7 ( 87.8 , 92.3)% . UTER24 was 192.3 ( 52.4 ) and 205.3 (58.0)mcg with a mean ratio ( 90 % CI ) of 93.7 ( 113.5 , 77.3)% . This urinary pharmacokinetic method to identity relative lung and systemic bioavailability between two nebuliser systems was easy to perform and is a useful and simple in vivo method to compare different nebulisers in patients receiving non-invasive ventilation Although the administration of beta(2)-agonists by inhalation is recommended in the current guidelines for treatment of patients with acute bronchospasm  , the large volume spacer that is necessary often is not available on board an ambulance due to space storage problems . Accordingly , an adapter enabling the application of therapeutic aerosols from a metered-dose inhaler ( MDI ) via a resuscitator bag ( Ambu MediBag ) was developed . The aim of this double-blinded , r and omised study was to test the clinical efficiency of the Ambu MediBag ( volume : approximately 1500 ml ) in comparison with the commonly used Volumatic-Spacer ( volume : 750 ml ) . One hundred patients receiving a bronchodilator response test were treated with MDIs of either 200 microg salbutamol via the Volumatic-Spacer or 400 microg salbutamol via the Ambu MediBag . The change of lung function variables was measured by bodyplethysmography before and after drug application . In both groups of 50 patients each , a highly significant reduction of airway resistance was shown after treatment . However , there was no statistically significant difference in lung function variables between the Ambu MediBag and the Volumatic-Spacer . From these results , we conclude that the Ambu MediBag is as effective as Volumatic-Spacer and might improve pre clinical and clinical treatment of acute bronchospasm by inhalation with bronchodilators OBJECTIVES In some acute-care setting s , practitioners are reluctant to institute bronchodilator therapy with metered-dose inhalers ( MDIs ) as st and ard management . Such therapy requires that personnel ensure optimal use of these devices . We prospect ively evaluated the time required to teach patients correct inhaler use for the emergency treatment of asthma and COPD , and patient factors associated with duration of teaching . DESIGN MDI arm within a single-center r and omized clinical trial comparing bronchodilator administration by MDI with a delivery enhancement device ( MDI/DED ) vs delivery by wet nebulizer . SETTING All subjects were treated for asthma or COPD exacerbations at the respiratory acute-care day hospital of the Montreal Chest Institute , immediately after presentation to our emergency department . Inhaler-use education was provided according to a predetermined protocol . MEASUREMENTS Subjects ' baseline characteristics were obtained from medical charts , spirometry , and question naires ; satisfaction was evaluated by question naire . All inhaler-use education was observed and timed . RESULTS Sixty-one patients with asthma ( median age , 46 years ) and 32 patients with COPD ( median age , 68.5 years ) were r and omized to treatment by MDI/DED . Mean FEV1 ( percent predicted ) was 63.5 % for patients with asthma and 39.5 % for patients with COPD . Five patients could not complete MDI teaching and therefore received subsequent treatment by wet nebulization . For the 88 other patients , the median teaching time was 6.5 min . Shorter teaching-time requirements were independently associated with higher initial arterial oxygen saturation , home DED use after previous MDI instruction , and a single initial bronchodilator treatment by wet nebulization . Most subjects expressed satisfaction with MDI/DED teaching and treatment . CONCLUSIONS Successful MDI/DED teaching followed by self-medication is feasible in the emergency setting , based on a simple protocol . A single bronchodilator dose administered by wet nebulization may facilitate subsequent MDI teaching Short-acting beta(2)-agonists are currently recommended for symptom relief in asthma and the treatment of mild , acute exacerbations in COPD . However , formoterol has as fast an onset of action as salbutamol with the additional benefit of longer-lasting bronchodilation ( approximately 12 h ) . Furthermore , systemic side effects observed with formoterol are of a similar duration but less pronounced than with short-acting beta(2)-agonists . In this double-blind , r and omized , cross-over study , 20 adult patients with reversible chronic airway obstruction ( intrinsic asthma or COPD ) inhaled single doses of formoterol 9 microg or salbutamol 100 microg ( group A ) or formoterol 18 microg or salbutamol 200 microg ( group B ) . FEV(1 ) was measured prior to and 5 , 10 , 15 , 20 , 25 and 30 min following inhalation of study drug . No significant differences in FEV(1 ) values were observed between group A ( P=0.704 ) or group B ( P=0.270 ) at baseline , or at 5 ( Group A : P=0.340 ; Group B : P=0.559 ) and 15 min ( Group A : P=0.526 ; Group B : P=0.818 ) post dose . No adverse events were reported during the study . Formoterol Turbuhaler has as rapid an onset of action as salbutamol pMDI when given at the recommended doses Traditionally , patients with acute airflow obstruction are treated with bronchodilator aerosols delivered by continuous flow nebulizers . While bronchodilator administration with the metered dose inhaler ( MDI ) and reservoir or spacer attachment is as effective as administration with the nebulizer in most setting s , the former has not been widely accepted for treatment of acute airway obstruction in the emergency room . We compared the efficacy of the continuous flow nebulizer to that of the MDI with InspirEase ( reservoir spacer ) in 75 patients ( 45 men and 30 women ) , ages 18 - 73 ( chi 44 years ) who presented to the emergency room with acute asthma and COPD . Subjects in each group ( 22 COPD and 53 asthma ) were r and omly assigned to treatment with three puffs of metaproterenol ( 0.65 mg/puff ) via the MDI with InspirEase plus nebulizer with placebo , or placebo MDI with InspirEase plus nebulizer with 15 mg metaproterenol in double blind fashion . Either treatment was given three times at 30 min intervals . The FEV1 and dyspnea scores according to the Borg scale were measured at baseline , 30 min after the first treatment , and 30 min after the third . There was no significant outcome difference between the two treatments in either diagnostic group . There also was no significant outcome difference for patients with baseline FEV1 less than 0.9L . Serum theophylline levels , the need for concomitant therapy with corticosteroids , or additional emergency room therapy after the study , hospitalizations and treatment side effects did not differ between treatment groups . We conclude that there is no demonstrable advantage of a continuous flow nebulizer over an MDI with InspirEase for the treatment of acute airflow obstruction PURPOSE Results of a prospect i ve study comparing clinical outcomes and costs of levalbuterol versus albuterol therapy for exacerbations of asthma or chronic obstructive pulmonary disease ( COPD ) are presented . METHODS In a single-center open-label study , selected adults hospitalized for asthma or COPD exacerbations over a 21-month period were r and omly assigned to receive levalbuterol 1.25 mg three times daily ( n = 55 ) or albuterol 2.5 mg four times daily ( n = 57 ) ; dosage reductions and other respiratory therapies were permitted . Study outcomes included scheduled and rescue nebulizations , total treatment costs , hospital length of stay , and change in heart rate from baseline . RESULTS The numbers of scheduled nebulizations were similar in the levalbuterol and albuterol groups ( mean ± S.D. , 19.6 ± 13.4 versus 20.7 ± 14.4 ; p = 0.692 ) , as were the numbers of rescue nebulizations ( mean ± S.D. , 0.7 ± 1.4 versus 0.8 ± 2.0 ; p = 0.849 ) . The mean change from baseline in heart rate did not differ significantly between groups . Mean total treatment costs per patient were significantly greater with the use of levalbuterol ( $ 8003 , bootstrap 95 % confidence interval [ CI ] , $ 6628-$9379 ) versus albuterol ( $ 5772 , bootstrap 95 % CI , $ 5051-$6494 ; p = 0.006 ) . Hospital length of stay was significantly greater in the levalbuterol group ( mean ± S.D. , 8.5 ± 5.2 days versus 6.8 ± 3.6 days with albuterol use ; p = 0.040 ) . CONCLUSION Clinical outcomes were similar with the use of levalbuterol versus albuterol for exacerbations of COPD or asthma . On average , patients receiving levalbuterol had longer and more costly hospital stays BACKGROUND : Exacerbations of COPD ( E COPD ) are characterized by increased dyspnea due to dynamic pulmonary hyperinflation . This study sought to determine whether the AeroEclipse II breath-activated nebulizer ( BAN ) would produce greater bronchodilator responses than a continuous flow small-volume nebulizer ( SVN ) in patients with E COPD . METHODS : Prospect i ve r and omized controlled trial . Forty patients with E COPD were recruited to participate in the trial . The primary study outcomes were inspiratory capacity ( IC ) and dyspnea via the Borg scale . Subjects were r and omized to receive bronchodilator from either a BAN or a continuous flow SVN . Subjects in both groups received 2.5 mg albuterol sulfate and 0.5 mg ipratropium bromide by nebulizer every 4 hours , and 2.5 mg albuterol every 2 hours as needed . Approximately 2 hours after the subject 's 6th scheduled nebulizer treatment , IC , dyspnea , and respiratory frequency measurements were repeated . RESULTS : Both groups received an equal number of nebulizer treatments over the study period ( BAN 6.25 ± 0.55 , control 6.2 ± 0.7 , P = .80 ) . Following completion of the study protocol the BAN group had a higher IC than the SVN group ( 1.83 ± 0.65 L vs 1.42 ± 0.49 L , P = .03 , respectively ) . The change in IC was higher in the BAN group ( 0.33 ± 0.31 L than in the SVN group ( 0.15 ± 0.19 L , P = .03 ) . The BAN group also had a lower respiratory rate ( 19 ± 3.3 breaths/min vs 22 ± 5.3 breaths/min , P = .03 , respectively ) . There was no difference in resting dyspnea as measured with the Borg scale ( BAN 3.3 ± 2.1 , SVN 3.5 ± 2.4 , P = .69 ) or stay ( BAN 4.6 ± 2.6 d , SVN 5.7 ± 2.8 d , P = .21 ) . CONCLUSIONS : In this cohort of patients with E COPD , a BAN was more effective in reducing lung hyperinflation and respiratory frequency than a continuous-flow SVN OBJECTIVE Compare the therapeutic efficacy of an oral/metered-dose inhaler ( oral/MDI ) regimen to an intravenous/nebulizer ( I.V./neb ) regimen of methylprednisolone , cefuroxime , and inhaled albuterol and ipratropium bromide in patients hospitalized for exacerbations of chronic obstructive pulmonary disease ( COPD ) . DESIGN R and omized , nonblinded , therapeutic trial . SETTING Two community hospitals in Bangor , Maine . PATIENTS 34 individuals with severe COPD . The mean admission forced expiratory volume in the first second was 0.75 L ( oral/MDI 0.78 L , I.V./neb 0.71 L ) . RESULTS Baseline demographic , laboratory , comorbidity , and ventilatory values determined in 19 patients who received the oral/MDI regimen and 15 patients treated with the I.V./neb regimen indicated comparability of the two groups . Outcome variables that compared oral/MDI to I.V./neb , including mean change in forced expiratory volume in the first second ( 0.12 L vs 0.13 L ) , mean length of stay ( 4.3 vs 5.1 d ) , and treatment failures ( 32 % vs 33 % ) , showed no significant differences . CONCLUSION Patients hospitalized for COPD exacerbations can be successfully ( and potentially less expensively ) treated with an oral/MDI treatment regimen Patients hospitalised for exacerbations contribute significantly to the total chronic obstructive pulmonary disease ( COPD ) -related healthcare costs . This study aim ed to determine the re source use and costs of exacerbations by exacerbation-severity and to identify risk factors for hospitalisation . Exacerbations and the details of all associated healthcare utilisation were recorded as part of a prospect i ve cost-effectiveness analysis linked to two r and omised controlled trials comparing tiotropium with ipratropium in 519 patients with stable COPD at study entry in the Netherl and s and Belgium .  Exacerbation-severity was rated by the physician . A Cox proportional hazards analysis was performed to identify independent risk factors of hospitalisation . Covariates that entered this analysis were smoking status , pack-years , body mass index , number of concomitant diseases , number of concomitant medications , use of inhaled steroids , physician visits prior to trial , FEV1 % predicted , quality of life , baseline dyspnea index ( BDI ) and treatment arm . The mean number of exacerbations per patient was 0.70 ( 95%-CI:0.60 , 0.81 ) . About 10 % of the exacerbations was severe , 47 % moderate and 43 % was mild . The mean costs of these exacerbations were Euro 4007 ( 95%-CI:2004 , 6011 ) , Euro 579 ( 390 , 768 ) and Euro 86 ( 49 , 124 ) , respectively . In addition to treatment arm , a body mass index below 18.5 ( RR:3.62 ) , each additional concomitant diagnosis ( RR:1.40 ) and a decrease of 1 point in the baseline dyspnea index ( RR:1.18 ) were significant risk factors of hospitalisation . Exacerbations that were associated with a hospitalisation accounted for 90 % of the total costs of exacerbations . Underweight , history of concomitant diseases and increased dyspnea ( BDI score ) are factors that are likely to identify patients who are at increased risk for generating high costs due to hospitalisation In 18 patients with chronic obstructive pulmonary disease intubated and mechanically ventilated , we prospect ively r and omized 200 micrograms fenoterol-80 micrograms ipratropium bromide ( four puffs ) from a metered-dose inhaler ( MDI ) versus 1.25 mg fenoterol-500 micrograms ipratropium bromide in 5 ml saline from a nebulizer ( NEB ) .  Respiratory mechanics were assessed before and 30 min after the end of each delivery by the rapid end-inspiratory airway occlusion technique . We did vary on single breaths the inflation flow ( V ) from 0.2 to 1.2 L. s-1 , at constant inflation volume . The total respiratory resistance of the respiratory system ( Rrs ) was partitioned into airway ( Rint , rs ) and tissue ( DeltaRrs ) resistances . We found that Rrs was equivalently reduced , from 16.49 + /- 1.37 to 14.85 + /- 1.88 cm H2O . L-1 . s with MDI ( p < 0.05 ) and from 18.04 + /- 1.85 to 15.15 + /- 1.33 cm H2O . L-1 . s with NEB ( p < 0.01 ) . Whereas the prevailing effect of MDI was to reduce Rint , rs , that of NEB was to decrease DeltaRrs . In addition , the V resistance of the respiratory system over the whole range of V was significantly affected by NEB but not by MDI The effectiveness of nebulized anticholinergic and sympathomimetic regimens was evaluated in a double-blind study of 199 patients with acute airways obstruction . Patients were assigned to one of three treatment regimens according to a r and omized schedule : 0.5 mg of ipratropium bromide , 1.25 mg of fenoterol hydrobromide , and 0.5 mg of ipratropium plus 1.25 mg of fenoterol . In 148 patients with acute exacerbations of asthma ( mean one-second forced expiratory volume , 1.18 + /- 0.64 liters ) , all three regimens produced significant improvement in one-second forced expiratory volume ( p less than 0.001 ) . The greatest improvement followed treatment with the  ipratropium-fenoterol combination ( 0.53 + /- 0.40 liters at 45 minutes ; 0.57 + /- 0.51 liters at 90 minutes ) and was significantly greater than that following either ipratropium alone ( p less than 0.001 ) or fenoterol alone ( p less than 0.05 ) . In 51 patients with acute exacerbations of chronic obstructive pulmonary disease ( mean one-second forced expiratory volume , 0.67 + /- 0.29 liter ) , each regimen produced significant improvement in one-second forced expiratory volume at both 45 and 90 minutes ( for all , p less than 0.05 ) , but there was no significant difference among the three treatment regimens . It is concluded that , in patients with acute asthma , combination therapy with sympathomimetic and anticholinergic agents is more efficacious than either one alone . In patients with acute exacerbations of chronic obstructive pulmonary disease , although either sympathomimetic or anticholinergic therapy provides bronchodilatation , no further benefit could be demonstrated from combination therapy This double-blind crossover study compared the efficacy of two methods of delivery ( MDI-spacer and nebulizer ) of inhaled albuterol to patients hospitalized for an acute exacerbation of COPD . Within 24 h of admission , 20 subjects ( mean age , 69 years ) with severe airflow obstruction ( mean FEV , 0.69 L ) were subjected to a treatment with an MDI-spacer ( 0.36 mg of albuterol or placebo ) followed by treatment with a nebulizer ( 2.5 mg of albuterol or placebo ) . Active drug was given by only one device ( r and omly assigned in a double-blind manner ) , and the entire sequence was repeated in 4 h , with active drug given in the alternate device . Spirometric data and the Borg dyspnea score were obtained before and 1 h after each sequence of treatments . Treatment result ed in significant improvements in the FEV1 , FVC , and Borg score . The percent improvement in the FEV1 was slightly larger after treatment with the nebulizer ( 16.7 percent vs 13.4 percent ) . Improvements in the Borg score were slightly larger after treatment with the MDI-spacer ( -1.08 vs -0.73 ) . However , these differences were not statistically significant . This study suggests that the MDI-spacer system is an effective method of sympathomimetic delivery in this setting , provided patients are able to master the technique We compared two modes of aerosol bronchodilator delivery in 34 patients hospitalized with obstructive airways diseases . The st and ard mode , therapist-administered up-draft nebulization ( UDN ) , is labor-intensive and therefore relatively costly . The alternative mode , self-administration by a metered dose inhaler ( MDI ) , is less costly , but its efficacy over an entire hospitalization has heretofore not been established . Patients were enrolled after transfer to the pulmonary ward from the emergency room or intensive care units ( ICU ) . We then r and omized them to receive metaproterenol q4h either via MDI or UDN . Daily spirometry revealed that MDI and UDN were associated with equivalent bronchodilation initially and equivalent improvement at discharge . The duration of hospitalization for the two groups was also the same . Thus , the two delivery methods were equally effective . We could not attribute this equivalence to pretreatment intergroup differences or to differences in concomitant therapy with steroids , theophylline , other bronchodilators , or antibiotics . Routine use of MDI rather than UDN in all non-ICU adult patients would save $ 253,487 per year at our institution alone OBJECTIVE To determine the efficacy of a metered-dose inhaler ( MDI ) with a large spacer device as compared to nebulized wet aerosols in the treatment of an unselected population with severe airflow limitation . DESIGN R and omized , double blind , placebo-controlled trial . SETTING University Hospital Department of Emergency Medicine ( DEM ) . PATIENTS Fifty patients , referred to the DEM between October 1 , 1994 and March 31 , 1995 with a severe , acute obstructive pulmonary event . Thirteen patients were diagnosed as having COPD ; 37 patients were diagnosed as having asthma . INTERVENTION AND RESULTS Patients received either placebo MDI through a 750-mL cone-shaped spacer ( Glaxo ) [ 2 puffs ] and nebulized salbutamol aerosol 0.5 mL in 1.5 mL saline solution ( group 1 , n=25 ) or salbutamol MDI and 0.5 mL saline solution in 1.5 mL saline solution administered in the same manner as above ( group 2 , n=25 ) . The above treatment was repeated three times every 15 min , unless side effects appeared . Upon enrollment into the study , the FEV1 in group 1 was 0.78+/-0.7 L ( mean+/-SD ) , 32 % of predicted , and in group 2 , 0.74+/-0.51 L , 29 % of predicted ( p=0.83 ) . The FEV1 values after the first , second , and third interventions were as follows : in group 1 , 1.18+/-0.99 L , 1.40+/-0.8 , and 1.47+/-0.79 , respectively , and in group 2 , 1.17+/-0.99 L , 1.46+/-1.01 , and 1.54+/-0.79 ( p=0.83 , 0.36 , and 0.48 , respectively ) . We observed no difference in spirometric measurements between the two groups at any time . CONCLUSION Even in the setting of the unselected group of patient referrals to the DEM for episodes of severe airflow limitation , the clinical and the objective bronchodilator responses to the administration of salbutamol are independent of the method of delivery : MDI with a large spacer vs aerosol nebulization STUDY OBJECTIVES Despite the widespread use of short-acting , inhaled beta(2)-agonists in acute exacerbations of COPD ( AE COPD s ) , little is known about their optimal dose . The aims of this study are to compare the bronchodilator response to incremental doses of inhaled albuterol during and after recovery from an AE COPD , and to compare the effects of regular nebulized albuterol , 2.5 mg and 5 mg , on the speed of recovery . METHODS Eighty-six patients admitted with an AE COPD were recruited . Each patient was administered incremental doses of inhaled albuterol on hospital admission and following recovery . Dose-response curves were constructed based on FEV(1 ) and peak expiratory flow rate ( PEFR ) recorded after each incremental dose . Patients were then r and omized in a double-blind fashion to receive 2.5 mg or 5 mg of nebulized albuterol q4h until recovery . Twice-daily PEFR , the number of extra doses of bronchodilators , and side effects reported were recorded . RESULTS Maximal bronchodilation ( Emax ) FEV(1 ) ( maximal bronchodilatory response to albuterol ) increased from 0.64 + /- 0.27 L/min during the exacerbation to 0.94 + /- 0.38 L/min during recovery ( p < 0.001 ) . The Emax PEFR increased from 147.53 + /- 62.46 L/min to 222.94 + /- 73.82 L/min after recovery ( p = < 0.001 ) . There was no significant difference in rate of recovery of PEFR ( p = 0.684 ) , duration of hospital stay ( p = 0.084 ) , or side effects ( p = 0.506 ) between the groups receiving 2.5 mg or 5 mg of nebulized albuterol . CONCLUSIONS There was significant improvement in Emax to inhaled albuterol as the COPD exacerbation resolved . There was no significant difference in outcomes including length of hospital stay or recovery of lung function between patients treated with regular 2.5 mg vs 5 mg of nebulized albuterol during an AE COPD This study compared the effect of " st and ard " dose metaproterenol delivered by h and -held nebulizer ( HHN ) with two puffs of metaproterenol delivered by a metered dose inhaler ( MDI ) via a spacer ( InspirEase ) ( MDI-spacer ) . Seventeen patients with an acute exacerbation of obstructive pulmonary disease were studied . Each patient received both MDI-spacer and HHN . Alternate patients were r and omized to either MDI-spacer or HHN as initial treatment . Each subject was tested four different times : before and 30 minutes after the initial aerosol delivery technique , and before and 30 minutes after the alternate aerosol delivery technique . Testing consisted of spirometry , lung auscultation , and measurement of vital signs . The interval between treatments for all subjects was 2.96 + /- 0.27 hours ( mean + /- SEM ) and was not different for subjects who received therapy via MDI-spacer first or HHN first . The patient population studied demonstrated  severe airways obstruction ( baseline FEV1 33.3 percent predicted + /- 4.9 percent ) . There was a statistically significant improvement in FVC and FEV1 after metaproterenol delivered by HHN , but not after MDI-spacer . Metaproterenol treatment with HHN result ed in a greater improvement in FEV1 ( p less than .05 ) than MDI-spacer when the data were reported as absolute improvement ( 0.19 + /- 0.05 L for HHN ) vs ( 0.06 + /- 0.03 L for MDI-spacer ) or reported as percent change ( 23.2 + /- 6.6 percent for HHN ) vs ( 9.5 + /- 3.4 percent for MDI-spacer ) . Asthmatic patients exhibited a significantly greater ( p less than 0.05 ) improvement in FEV1 after HHN ( 23.4 + /- 4.7 percent change ) than after MDI-spacer ( 6.6 + /- 4.5 percent change ) . Patients with chronic obstructive pulmonary disease ( COPD ) exhibited a greater improvement in FVC ( p less than 0.05 ) after HHN ( 25.2 + /- 6.7 percent change ) than after MDI-spacer ( 5.8 + /- 4.7 percent change ) . We conclude that the " st and ard " dosage of metaproterenol delivered by HHN results in greater spirometric improvement in patients with acute obstructive pulmonary disease than the conventional dosage of metaproterenol delivered by MDI-spacer . It is likely that this reflects the fact that the recommended dose of metaproterenol delivered by MDI is too low and should be increased Two double-blind , placebo-controlled studies were performed in patients with chronic , partially reversible airflow limitation to compare ipratropium bromide and fenoterol administered singly with the combination treatment . In the first study , ipratropium bromide , 40 micrograms , or placebo was administered 2 h before fenoterol , 400 micrograms , or placebo , both by metered-dose inhaler . The combined treatment demonstrated significant additive bronchodilatation with an improved forced expiratory volume in 1 s ( FEV1 ) response from 3 to 6 h after fenoterol administration . In the second study , ipratropium bromide , 0.5 mg , fenoterol , 2.0 mg , or placebo was administered by aerosolized solution with a nebulizer . The FEV1 response to the combined treatment , administered at the same time , was significantly greater than for fenoterol ( 0.5 , 0.75 , 4 and 6 h ) and for ipratropium bromide ( 0.25 - 1.5 , and 4 h ) at various times . There was a disproportionate increase in forced vital capacity ( FVC ) compared with FEV1 for all treatments , suggesting dilatation and increased stability of small airways . In both studies , no synergistic effect is implied . In summary , additive bronchodilatation may be achieved with combined ipratropium bromide and fenoterol treatment by metered-dose inhaler or aerosolized solution Some clinical trials have suggested that the inhaled long-acting β2-agonists ( LABAs ) may be effective in the treatment of acute exacerbations of chronic obstructive pulmonary disease ( AE COPD ) . Since indacaterol , the first once-daily LABA to be developed for the regular treatment of COPD , exhibits fast onset of action and 24-h duration of bronchodilation , we have investigated its effects in patients with AE COPD managed in the emergency department . In a r and omised controlled pilot trial , we have enrolled 29 consecutive patients with a recent ( i.e. , within ≤ 4 d ) history of AE COPD and requiring hospitalization . All patients received a st and ard protocol consisting of ipratropium bromide aerosol 500 μg three times a day , intravenous methylprednisolone 20 mg twice-daily and , if indicated , oral levofloxacin 500 mg once-daily . Moreover , they were r and omly allocated to one of the two 5-day treatment groups ( indacaterol maleate 300 μg once-daily or salbutamol nebulizer 1250 μg three times a day ) . The administration of indacaterol 300 μg to patients admitted to emergency department for an AE COPD result ed in a greater improvement of pulmonary function compared with traditional therapy , without cardiovascular side effects . Our results suggest that indacaterol could be a useful option in the treatment of AE COPD . However , further larger double-blinded r and omized clinical trials are needed to vali date the intriguing results obtained in this setting
BACKGROUND Bronchodilators are a central component for treating exacerbations of chronic obstructive pulmonary disease ( COPD ) all over the world .
Clinicians often use nebulisers as a mode of delivery , especially in the acute setting , and many patients seem to benefit from them .
However , evidence supporting this choice from systematic analysis is sparse , and available data are frequently biased by the inclusion of asthma patients .
Therefore , there is little or no formal guidance regarding the mode of delivery , which has led to a wide variation in practice between and within countries and even among doctors in the same hospital .
We assessed the available r and omised controlled trials ( RCTs ) to help guide practice in a more uniform way .
OBJECTIVES To compare the effects of nebulisers versus pressurised metered dose inhalers ( pMDI ) plus spacer or dry powder inhalers ( DPI ) in bronchodilator therapy for exacerbations of COPD .