TABLE 1.
The characteristics of the included studies.
| Author | Number of participants (bacterial lysate/control) | Major inclusive criteria | Study design | Type of bacteria lysate | Administration way | Dosages and session | ||
| Avdeev et al. (8) | 30/30 | Patients with frequent exacerbations of COPD (group C and D according to the GOLD classification) | Parallel RCT, multicenter | Ismigen | Sub-lingual | A cycle consisted of sublingual consumption of one tablet per day for 10 consecutive days, followed by 20 days of standard treatment for three consecutive months | ||
| Zeng et al. (14) | 78/72 | Stable COPD patients | Parallel RCT, single center | OM-85 | Oral | A capsule (OM-85 7 mg) or placebo daily for 10 consecutive days per month, for 6 consecutive months | ||
| Tang et al. (9) | 192/192 | Age 40–75 years, male or female, physician-diagnosed chronic bronchitis, or COPD (for 6 months) suffering from an acute exacerbation according to the GOLD definition at enrollment and an FEV1 between 40 and 70% of the predicted value within the 6 months before enrollment. | Parallel RCT, multicenter | OM-85 | Oral | One capsule (OM-85 7 mg) or placebo daily for 10 consecutive days per month, for 3 consecutive months (12 weeks) | ||
| Braido et al. (10) | 146/142 | A documented diagnosis of moderate, severe or very severe COPD, according to the GOLD 2006 | Parellel RCT, multicenter | Ismigen | Sub-lingual | A cycle consisted of sublingual consumption of one tablet per day for 10 consecutive days, followed by 20 days of standard treatment for 3 consecutive months. After 3 months without any PMBL treatment, a second cycle of therapy (as described above) was undertaken. At the end of the second treatment period, a second three-month period without PMBL was observed | ||
| Ricci et al. (13) | 12/11 | Patients aged 40 years or older with documented moderate, severe or very severe COPD | Parellel RCT, single center | Ismigen | Sub-lingual | A cycle of 90-day treatment wherein the first 10 days of each 30 days 1 tablet of either PMBL or placebo was given. This was followed by a 90-day ‘rest’ period (no treatment). | ||
| Nishantha et al. (15) | 24/21 | Stable COPD patients with moderately severe or severe disease staging, presenting during May – September 2012 | Parallel RCT, single center | Ismigen | Sub-lingual | Daily on the first 10 days of three successive months | ||
| Olivieri (16) | 340 | Patients aged over 40 years old, with COPD stage II or III, with a history of at least 2 documented AE-COPD in the previous year, and an FEV1 between 30 and 80% | Parallel RCT, multicenter | OM-85 | Oral | A capsule daily during month 1, and 1 capsule daily for 10 days in months 3–5. | ||
| Cazzola et al. (17) | 33/30 | Patients suffering from moderate-to-very severe COPD, who were under regular treatment with salmeterol/fluticasone (SFC) 50/500 mg BID | Parellel RCT, single center | Ismigen | Sub-lingual | one capsule daily the first 10 days of three consecutive months | ||
| Solèr et al. (18) | 142/131 | Outpatients aged 40 years old of both sexes with a history of chronic bronchitis or mild COPD at the time of an AE | Parallel RCT, multicenter | OM-85 | Oral | A capsule of OM-85 or placebo per day for 30 days, followed by three 10-day courses for months 3, 4, and 5 | ||
| Li et al. (19) | 49/41 | Patients with chronic bronchitis complicated with COPD | Parallel RCT, multicenter | OM-85 | Oral | A capsule daily for the first 10 days of each month for 3 consecutive months | ||
| Collet et al. (20) | 191/190 | Patients with a history of heavy smoking and an FEV1 value between 20 and 70% of predicted | Parallel RCT, multicenter | OM-85 | Oral | A capsule per day for 30 days followed by a repeat course of 10 consecutive days of therapy per month for 3 months | ||
| Xinogalos et al. (21) | 33/29 | – | Parellel RCT, multicenter | OM-85 | Oral | A capsule (7 mg)/day for 1 month; 1 capsule/10 days for months 3, 4, and 5 | ||
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| Author | Control | Outcomes | Study period | Follow up | Treatment duration | Drop up | Registration number | Country |
|
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| Avdeev et al. (8) | Blank | The severity of symptoms, frequency of recurrence of COPD exacerbations, readmissions, need for emergency care and changes in basic therapy of COPD | NR | 3 months | 3 months | NR | NR | Russia |
| Zeng et al. (14) | Blank | The number of acute exacerbations per person per year, quality of life, lung function, T cell subsets | 2015.07–2016.07 | 6 months | 6 months | NR | NR | China |
| Tang et al. (9) | Placebo | The proportion of patients with recurrent acute exacerbations during the 12-week treatment period. Secondary efficacy endpoints included the proportion of patients with recurrent acute exacerbations over the 22-week study period, the proportion of patients treated | 2005–2008 | 10 weeks | 12 weeks | 19 (4.9%) | China Food and Drug Administration TG0504BCV | China |
| Braido et al. (10) | Placebo | The primary outcome is the number of exacerbations, the secondary outcome is the time from the randomization to the first exacerbation, the average interval between the first and second exacerbation, the effects of Ismigen on symptoms | July 31, 2009, to June 16, 2012 | 3 months | 3 months, 2 cycle | NR | EudraCT 2007-000006-67 | Italy |
| Ricci et al. (13) | Placebo | Serological changes, exacerbation rate and symptom | Fall in 2019 to fall in 2010 | About 3 months | 3 months | 0 | NR | Italy |
| Nishantha et al. (15) | Placebo | Infective exacerbations and symptoms improvements | 2012 | 6 months | NR | NR | NR | Sri Lanka |
| Olivieri (16) | Placebo | The rate and duration of AECOPD, the rate of treatment-emergent adverse events | 2011 | NR | NR | NR | NR | NR |
| Cazzola et al. (17) | Blank | Symptoms, diagnosis of exacerbation, concomitant medications and hospitalization | Begin from September 2007 | 3 months | 3 months | 0 | NR | Italy |
| Solèr et al. (18) | Placebo | The primary endpoint was the mean rate of AEs occurring within the study period | NR | 1 month | 5 months | 40 (14.65%) | NR | Switzerland and Germany |
| Li et al. (19) | Placebo | The frequency of acute exacerbation, symptom scores, and lung function were recorded | NR | 9 months | 3 month | 0 | NR | China |
| Collet et al. (20) | Placebo | The primary outcome was the occurrence of at least one such episode during the 6 months. Secondary outcomes included total number of acute exacerbations and hospitalization for a respiratory problem, as well as all hospitalization, change in baseline respiratory symptoms, and change in quality of life | Begin from November 07, 1994 | 2 months | 4 months | 15 (3.93%) | NR | Canada |
| Xinogalos et al. (21) | Placebo | Clinical manifestations, frequency, duration and severity of acute exacerbations, consumption of conventional medications and serum immunoglobulin levels | Autumn/winter of 1990–1991 | 2 months | 4 months | – | – | – |
COPD, chronic obstructive pulmonary disease; GOLD, the global initiative for chronic obstructive lung disease; NR, not reported.