Two Different Dosages of Nebulized Steroid Versus Parenteral Steroid in the Management of COPD Exacerbations
Two Different Dosages of Nebulized Steroid Versus Parenteral Steroid in the Management of COPD Exacerbations
Chronic obstructive pulmonary disease (COPD) is a common disease that has a chronic and
 progressive course. Patients with COPD may have exacerbations one to four times in a year.
 Numbers of exacerbations are important because of increased morbidity and mortality and
 healthcare costs.

 Systemic corticosteroids (SC) are recommended in the management of exacerbations of COPD as
 well as bronchodilator, oxygen and antibacterial treatment by all international guidelines.
 However, there are still some concerns about systemic corticosteroid use because COPD
 patients are older and relatively immobilized. In addition, exacerbation rate is
 significantly higher in a group of COPD patients, and these patients need higher amounts of
 SC in order to control of exacerbation. It results in some adverse effects such as
 osteoporosis and bone fractures, thinning of the skin, posterior subcapsular cataract
 formation, glucose intolerance and myopathy. Thus, this condition leads clinicians to seek
 alternative options. However, there are few studies showing that nebulized steroids (NS) are
 as effective as SC in exacerbations of COPD and the optimal NS dose is not certain.

 The investigators aimed to determine the optimal NS dose and evaluate the efficacy and safety
 of NS compared with SC in the treatment of patients with COPD exacerbations requiring
 hospitalization.
Study Population One hundred twenty patients with moderate or severe COPD exacerbation who
 are older than 40-years-old, had a smoking history of at least 10-pack-years and requiring
 hospitalization were included in the study. COPD diagnosis was based on clinical evaluation
 as defined by the American Thoracic Society (ATS). The patients were excluded if they had a
 presence of asthma, allergic rhinitis, atopy or any systemic disease (such as diabetes
 mellitus or hypertension); were exposed to systemic corticosteroids in the preceding month;
 used more than 1,500 microg/d of inhaled beclomethasone equivalent; were admission to the
 intensive care unit (pH<7.30 and/or arterial partial pressure of carbon dioxide (PaCO2) > 70
 mm Hg, and/or arterial partial pressure of oxygen (PaO2) < 50 mm Hg despite supplemental
 oxygen); if a specific cause for the exacerbation, such as pneumonia, pneumothorax, or heart
 failure, was diagnosed.

 Study Design The study was as a randomized, double-blind, parallel design trial. The
 randomization order was determined using a computer-generated list of random numbers.
 Eligible patients were randomly allocated to one of the three treatment groups, that is,
 parenteral corticosteroid (PS), 4 mg nebulized budesonide (NB) or 8 mg NB. The efficacy of
 the study medications was assessed at hospitalization, 24 h, 48 h and before discharge.
 Patients were monitored during the hospitalization. Patients were withdrawn from the study if
 they required intubation and managed in intensive care unit.

 Treatments Treatment in the PS group consisted of methylprednisolone 40 mg (intravenous
 ampoule); treatment in the NB groups consisted of nebulized budesonide suspension (Pulmicort
 nebuampul® 0.5 mg/ml; Astra-Zeneca Pharmaceutical Production) for 10 days. Budesonide were
 given as 2 mg twice daily or 4 mg twice daily; methylprednisolone were given once daily
 intravenously.

 Nebulization procedures were performed by jet nebulizer (Porta Neb® Ventstream® 1803;
 Medic-Aid) with 80% of output of less than 5 micron. Patients received standard treatment
 with a nebulized ß-agonist (salbutamol 3.01 mg) and anticholinergic (ipratropium bromide 0.5
 mg) combination every 6 hours, intravenous aminophylline (0.5 mg/kg/h) and oral or
 intravenous antibacterial at the discretion of the attending physician. Supplementary oxygen
 therapy was used to maintain oxygen saturation (SaO2) >90%.

 Measurements Patients were assessed every 12 h during the acute phase (from H0 to H48), and
 at hospital discharge. Arterial blood samples were taken at baseline, 24, 48 h and before
 discharge for the determination of PaO2, PaCO2, and pH, regardless of whether the patient was
 on room air or on supplementary oxygen. Spirometry (Sensor Medics, Vmax22) was carried out
 before and 15 to 20 min after bronchodilator nebulization (ß2-agonist and ipratropium
 bromide) according to ATS standards. Dyspnea was assessed according to the modified Borg
 scale. Complete blood cell counts were obtained at entry, and blood glucose, sodium,
 potassium were measured at H0 and H48.

 Endpoints The primary endpoint was to assess treatment efficacy by the change of arterial
 blood gases from H0 to H24, H48 and before discharge. Secondary endpoints included the
 changes in FEV1 (forced expiratory volume in 1 second), dyspnea score, duration of
 hospitalization, and occurrence of adverse events. An adverse event was defined as any
 medical event reported by the attending physician and events resulting in treatment change,
 discontinuation study medication or prolonged of hospitalization.
Inclusion Criteria:

 -  Patients with moderate or severe COPD exacerbation who are older than 40-years-old

 -  A smoking history of at least 10-pack-years

 -  Requiring hospitalization because of COPD exacerbation

 Exclusion Criteria:

 -  Presence of asthma, allergic rhinitis, atopy or any systemic disease (such as diabetes
 mellitus or hypertension)

 -  Exposed to systemic corticosteroids in the preceding month or used more than 1,500
 microg/d of inhaled beclomethasone equivalent

 -  Admission to the intensive care unit (pH<7.30 and/or PaCO2 > 70 mm Hg, and/or PaO2 <
 50 mm Hg despite supplemental oxygen)

 -  If a specific cause for the exacerbation, such as pneumonia, pneumothorax, or heart
 failure, was diagnosed.