Two Different Dosages of Nebulized Steroid Versus Parenteral Steroid in the Management of COPD Exacerbations
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Budesonide 4 mg; Budesonide 8 mg; Metil prednisolone
Intervention type(s): Drug; Drug; Drug
Intervention description(s): It will be evaluated at baseline, 24 h, 48 h and before discharge; Baseline FEV1 and before discharge FEV1 were evaluated
Intervention MeSH terms: Prednisolone; Budesonide
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: COPD exacerbation; Nebulized budesonide; Parenteral steroid