. 2020 Aug 25;2020(8):CD013113. doi: 10.1002/14651858.CD013113.pub2

Sasaki 2009.

*Study characteristics*
Methods	Design: single‐blinded, multicentre randomised controlled trial Study duration: 12 months (October 2005 to March 2007) Number of study centres and location: four; Japan Setting: hospital outpatients (three secondary care hospitals and one tertiary care hospital) Withdrawals: PPI plus usual care: n = 1; usual care alone: n = 2
Participants	Number randomised: 103 participants with COPD (PPI plus usual care: n = 51; usual care alone: n = 52) Mean age (SD), age range: PPI plus usual care: 74.9 (8.9), range not reported; usual care alone: 74.8 (7.5), range not reported Gender, n (%) female: PPI plus usual care: 3 (6); usual care alone: 2 (4) Severity of COPD (Grade 1/2/3/4): PPI plus usual care: 16/14/17/3; usual care alone: 11/18/20/1 Diagnostic criteria: American Thoracic Society (ATS) for COPD Follow‐up duration: 12 months Baseline lung function: Mean (SD) stable state FEV₁ (L): PPI plus usual care: 2.13 (0.8); usual care alone: 2.20 (0.88) Mean (SD) FEV₁% predicted: PPI plus usual care: 66 (20); usual care alone: 75 (23) Mean (SD) FEV₁/FVC ratio (FEV₁%): PPI plus usual care: 58.7 (16); usual care alone: 62.0 (15.7) Smoking history (mean pack years): PPI plus usual care: 56; usual care alone: 50 Inclusion criteria: not stated Exclusion criteria: People with obvious bronchial asthma, bronchiectasis, or diffuse panbronchiolitis were excluded from the trial. People with active gastric or duodenal ulcers and GERD, and with symptoms of these diseases, were also excluded. People with QUEST scores of more than 6 points were defined as positive for GERD symptoms, and were excluded from this study.
Interventions	Intervention: PPI (lansoprazole) plus usual care* Comparison: usual care* alone Concomitant medications: not stated Excluded medications: not stated Dosage of the intervention: 15 mg daily *Usual care: participants were treated with bronchodilators, including sustained release theophylline, beta‐2 agonists, inhaled anticholinergic agents, and smoking cessation. Some of the participants with Stage III and IV COPD received inhaled corticosteroids because of frequent exacerbations of COPD.
Outcomes	Outcomes: The rate and number of common colds The following 10 cold‐related symptoms were recorded: sneezing, nasal discharge, nasal congestion, malaise, headache, chills, feverishness, sore throat, hoarseness, and cough. Symptoms were rated for severity on a scale from 0 to 3 and were recorded on daily record cards. A daily total of the symptom scores could vary from 0 to 30. A common cold was defined as a total symptom score greater than 5. The rate and number of COPD exacerbations Exacerbations were defined as an acute and sustained worsening of COPD symptoms requiring changes to regular treatment, including antimicrobial therapy and short courses of systemic corticosteroids. Time point: 12 months
Notes	Funding: Ministry of Health, Labour and Welfare, Japan; Ministry of Education, Science, Culture, Sports, Science and Technology (19590690; 19790455); Japanese Foundation for Aging and Health Notable author conflicts of interest: Dr Yamaya was partly supported by Health and Labour Sciences Research Grants for Research on Measures for Intractable Diseases from the Ministry of Health, Labour and Welfare (H20nannchiippann35) and the Respiratory Failure Research Group from the Ministry of Health, Labour and Welfare, Japan. Dr Nakayama was partly supported by a Grant‐in‐Aid for Scientific Research from the Ministry of Education, Science, Culture, Sports, Science and Technology (19590690) and a grant from the Japanese Foundation for Aging and Health. Dr Sasaki was partly supported by a Grant‐in‐Aid for Scientific Research from the Ministry of Education, Science, Culture, Sports, Science and Technology (19790455). This work was supported by these grants. The other co‐authors do not have any potential conflicts of interest.
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "Randomization was performed using a random number table."
Allocation concealment (selection bias)	Unclear risk	Quote: "Randomization was performed using a random number table, and the list was held independently of the investigators."　 Since it was not clearly stated whether the concealment was maintained we judged it as an unclear risk.
Blinding of participants and personnel (performance bias) All outcomes	High risk	Participants and study personnel remained unblinded to treatment allocation.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Described as observer‐blinded, but details about the exact role of the observers were not provided.
Incomplete outcome data (attrition bias) All outcomes	Low risk	During trial: 1/51 withdrew from the intervention group; 2/52 withdrew from the control group. Although a total of 103 people were randomised, 3 losses at follow‐up were excluded from the analysis and no details were given. We contacted the author and confirmed that it was done with per‐protocol rather than ITT analysis. However, we thought that the dropout rate was small so the impact on the results was small and the risk of bias was low.
Selective reporting (reporting bias)	Unclear risk	The trial was not preregistered on any appropriate clinical trial registries; study protocol not available.
Other bias	Low risk	Baseline imbalances in disease severity: participants in the intervention group appeared to have less severe disease (COPD grade I/II/III/IV: Intervention group: 16/14/17/3; control group: 11/18/20/1). However, randomisation method was appropriate and it was unlikely to have a significant effect on the results, thus the risk of other bias was low.

COPD: chronic obstructive pulmonary disease; FEV₁: forced expiratory volume in one second; FVC: forced vital capacity; GERD: gastroesophageal disease; PPI: proton pump inhibitor; QUEST: Quality of Upper Extremity Skills Test; SD: standard deviation; ITT: intention‐to‐treat.