Methods

Type: Parallel group.
Duration: 7 days or duration of hospitalisation (lesser of).
Randomization: blocks of 4, computer generated.
Outcome blinding: Double‐blind.
Co‐interventions: salbutamol 5mg QID, ipratropium 0.5mg QID, prednisone 40mg one time a day, oral antibiotic (if purulent sputum).
Confounders: none noted.
Assessment score: 5

Participants

Setting: Medical ward.
Inclusion criteria: Admission for acute COPD exacerbation, age >= 50 years, smoked >= 20 packyears, FEV1 on admission <= 1.5L.
Exclusion criteria: Use of theophylline in prior week or need for IV aminophylline, dx of pneumonia or congestive heart failure, prior dx of asthma, bronchiectasis, carcinoma, interstitial lung disease, paroxysmal atrial fibrillation or intolerance to theophylline.
Number recruited: 50
Mean age: 71 years
Gender: 46% male
Baseline FEV1: 0.6 L

Interventions

Experimental: longacting oral theophylline (Neulin‐24, 3M) 200mg or greater titrated to serum theo level of 10‐20 mg/L
Control: Placebo.

Outcomes

Analysed: Change in FEV1 at 3 days, length‐of‐stay, change in symptom scores, adverse effects. Reported: Change in FVC, Sa02
Mortality: None
Morbidity: Experimental group; myocardial infarction (1), non‐malignant tachycardia (2); Control group; none.

Notes

Likelihood of COPD: Stringent spirometry criteria

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

Information not available

Methods

Type: Parallel group.
Duration: 72 hrs. Randomization: block.
Outcome blinding: Double‐blinded, with the exception of one investigator who adjusted theophylline and placebo infusion rates.
Co‐interventions: 0.3mL of 5% Metaproterenol sulfate/2.5mL of normal saline q4hrs; methylprednisolone 0.5mg/kg q6hrs, Ampicillin 500mg q6hrs, O2 prn.
Confounders: None identified.
Assessment score: 5

Participants

Setting: ED/medical walk‐in.
Inclusion criteria: Prior diagnosis of COPD, prior spirometry of FEV1 < 2 SD below predicted and FEV1/FVC <60%, current diagnosis of COPD exacerbation requiring hospitalization.
Exclusion criteria: Prior diagnosis of asthma, readily reversible exacerbations, prior bronchodilator response of >30% change in FEV1, left heart failure, pneumonia, intubated.
Number recruited: 30
Mean age: 65 years
Gender: 96% male
Baseline FEV1: 0.6 L

Interventions

Experimental: IV aminophylline 0‐6mg/kg load (based on prior theo use), 0.5mg/kg maintenance infusion for level of 72‐94 umol/L (abstract lists 72‐83 umol/L).
Control: Placebo solution.

Outcomes

Analysed: Change in FEV1, dyspnea index, adverse effects.
Reported: Change in FVC, pO2 and pCO2.
Others: None
Mortality: None
Morbidity: Experimental group; intubation (1), Control group; intubation (1).

Notes

Likelihood of COPD: Stringent spirometry criteria

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

Information not available

Methods

Type: Parallel group.
Duration: 2 hours. Randomization: random number generator.
Outcome blinding: Double‐blinded.
Co‐interventions: 0.3 ml metaproterenol sulfate/2.5 ml saline nebulizer, 28% O2.
Confounders: Treating physician could break randomization code if necessary.
Assessment score: 4

Participants

Setting: ED.
Inclusion criteria: ATS definition of chronic bronchitis (1962).
Exclusion criteria: Febrile (>37.5 C), direct admission, arrhythmia, pneumonia, congestive heart failure.
Number recruited: 52
Mean age: 63 years
Gender: 100% male
Baseline FEV1: 0.8 L

Interventions

Experimental: IV aminophylline 2.8‐5.6mg/kg over 1 hour (based on prior theophylline exposure).
Control: D5W.

Outcomes

Analysed: Change in FEV1 at 2 hours, returns to ED in one week.
Reported: 17 patients hospitalised within 1 week, but not reported by treatment group
6‐month mortality: Experimental (3), Control (5)
Morbidity: "No significant side effects observed"

Notes

Likelihood of COPD: Clinical diagnosis of chronic bronchitis, baseline FEV1 0.8 L.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

Information not available

Methods

Type: Parallel group.
Duration: Until discharge from ED.
Randomization: yes.
Outcome blinding: Double‐blind.
Co‐interventions: 0.3 ml metaproterenol sulfate/2.5 ml saline nebuliser q30 min prn, methylprednisolone 80mg IV once, 28% O2.
Confounders:
Randomization not stratified by type of obstructive airways disease. Assessment score: 4

Participants

Setting: ED.
Inclusion criteria: asthma exacerbation or wheeze, age >45 years, smoking history of 20 pack‐years, duration of disease >20 years OR disease onset after age 45 years.
Exclusion criteria: Theophylline use in prior 24 hrs, adverse reaction to theophylline, corticosteroids, or beta‐agonists, type 1 diabetes mellitus, possible myocardial infarction, pulmonary edema.
Number recruited: 39
Mean age: 62 years
Gender: 64% male
Baseline FEV1: 0.7 L

Interventions

Experimental: intravenous aminophylline 5.6mg/kg over 20 minutes, then 0.9mg/kg constant infusion.
Control: Placebo.

Outcomes

Analysed: Change in FEV1, PEFR, hospitalizations, return to ED in 3 days, adverse effects
Reported: Change in FVC. Approximate costs, emergency department LOS
Mortality: None reported
Morbidity: Experimental group; new T‐wave inversions on EKG + hyperglycemia (1), Control group; none.

Notes

Likelihood of COPD: No prior PFT data; likely some misclassification with asthma since asthma/COPD subgroups established post hoc. Hospitalization decision made by non‐investigator with prespecified criteria.

Risk of bias

Bias

Authors' judgement

Support for judgement

Allocation concealment?

Unclear risk

Information not available