Probiotics in COPD: Effects on Symptoms, Lung Function, and Inflammation

Official title

"The Effect of Probiotics on the Degree of Dyspnea, Lung Function, and Inflammatory Mediators in Patients With Chronic Obstructive Pulmonary Disease (COPD)."

Overview

The goal of this randomized, placebo controlled, double-blind clinical trial is to find out whether a probiotic supplement can help adults with chronic obstructive pulmonary disease (COPD) breathe better and better control their symptoms. The study will try to answer does taking a probiotic supplement, compare with a placebo, reduce shortness of breath, does it improve daily COPD symptoms or change stool patterns by using validated questionnaires; does it affect lung function or inflammation. The results of this study may contribute to a better understanding of the disease, the application of new therapeutic options, and provide a foundation for future research.

Detailed description

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition characterized by persistent symptoms such as shortness of breath, chronic cough, sputum production, and periods of acute worsening. It is also associated with ongoing systemic inflammation, which contributes to symptom severity, impaired lung function, and increased risk of exacerbations. Emerging evidence suggests that the gut-lung axis may play a significant role in this inflammatory process. Probiotics, which help restore a healthy microbial balance and support gut barrier integrity, have been proposed as a potential strategy to modulate inflammation and respiratory symptoms. Several studies have suggested that probiotics may reduce respiratory symptoms, improve lung function and lower systemic inflammation in people with COPD.

This randomized study is designed to evaluate whether a probiotic supplement (Saccharomyces boulardii, Lactobacillus plantarum LP 6596, and Lactobacillus plantarum HEAL9) can improve shortness of breath, overall symptom burden, lung function, and selected inflammatory markers in adults with stable COPD compared with placebo. Participants will be recruited from multiple clinical centers and will continue their usual COPD therapy throughout the study period. A total of 60 adult participants with a confirmed diagnosis of COPD, stable disease and baseline dyspnea of mMRC (modified Medical Research Council) ≥ 1 will be randomized to receive either a probiotic supplement or placebo for 16 weeks. They will take either the probiotic supplement or placebo 2 capsules once daily for 16 weeks and will be examined at three clinic visits for symptom questionnaires- mMRC scale of dyspnea, CAT (COPD Assessment Test) and Bristol Stool Scale, blood sampling, and spirometry testing. Between clinic visits, participants will have regular telephone checks every 4 weeks to assess symptoms, adherence to the study product and possible side effects.

This trial aims to provide a more comprehensive understanding of how probiotic supplementation may influence dyspnea, quality of life, inflammatory activity, and respiratory function in COPD.

Interventions

• Dietary supplement Probiotic Capsule
  The participants will take two probiotic capsules per day for 16 weeks, containing S. boulardii, Lactobacillus plantarum LP 6596, and Lactobacillus plantarum HEAL9. The product will be coded for blinding purposes.
• Dietary supplement placebo capsule
  Participants will receive two capsules per day for 16 weeks, a placebo preparation that is identical in composition and form to the probiotic but does not contain an active substance. The product will be coded for blinding purposes.

Primary outcome measures

• mMRC scale of dyspnea [Time frame: 8 weeks]

Secondary outcome measures (12)

• CAT questionnaire [Time frame: 8, 16 weeks]
• Bristol stool scale [Time frame: 8, 16 weeks]
• mMRC [Time frame: 4,12,16 weeks]
• IL-6 [Time frame: 8 weeks]
• Complete blood count [Time frame: 8 and 16 weeks]
• Fibrinogen [Time frame: 8 and 16 weeks]
• CRP [Time frame: 8 and 16 weeks]
• Metabolic blood parameters-glucose [Time frame: 8, 16 weeks]
• Metabolic blood parameters-urea [Time frame: 8, 16 weeks]
• Metabolic blood parameters-creatinine [Time frame: 8, 16 weeks]
• Metabolic blood parameters-liver enzymes [Time frame: 8, 16 weeks]
• Metabolic blood parameters-electrolytes [Time frame: 8, 16 weeks]

Eligibility criteria

Inclusion criteria

• Patients with a previously established diagnosis of COPD, regardless of the degree of airflow obstruction on pulmonary function testing.
• Age over 18 years, regardless of sex.
• Stable disease without exacerbations during the past two months (8 weeks).
• Stable disease without changes to maintenance therapy during the past two months (8 weeks).
• Patients with an mMRC score of 1 or higher.
• Signed informed consent.

Exclusion criteria

• patients diagnosed with serious comorbidities such as severe cardiovascular diseases (severe heart failure, acute coronary syndrome, or percutaneous coronary intervention within 6 months, uncontrolled tachy/bradyarrhythmias), patients with severe renal failure and a placed central venous catheter, patients with severe liver damage (Child-Pugh class C), patients with infectious hepatitis or HIV, active bloody diarrhea;
• patients undergoing active oncological and hematological treatment;
• patients who have had a stroke within the past 3 months;
• transplanted patients, including allograft recipients;
• patients on long-term systemic corticosteroid and immunosuppressive therapy (oral or intravenous form) as well as antifungal therapy,
• patients who have had a COPD exacerbation within the past two months and are not in a stable condition,
• patients diagnosed with asthma,
• patients with a history of lung surgery or serious respiratory diseases other than COPD (active tuberculosis, sarcoidosis, pulmonary fibrosis, severe bronchiectasis, pulmonary aspergillosis, etc.),
• patients who have recently participated in other clinical trials or have received experimental therapy,
• patients with a history of severe allergic reactions or hypersensitivity to the components of the probiotic preparation,
• patients with active alcoholism or drug addiction,
• patients with severe psychiatric diagnoses or those with significant physical or cognitive limitations that would interfere with following the study protocol,
• patients who have recently undergone surgery,
• pregnant or breastfeeding women,
• patients who have taken any probiotic preparations within one month before the start of the study,
• patients whose COPD treatment is changed during the course of the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Croatia · 5 centers

• General Hospital Karlovac — Karlovac
• University Hospital Split — Split
• General Hospital Sibenik — Šibenik
• General Hospital Vinkovci — Vinkovci
• University Hospital Centre Sestre milosrdnice — Zagreb

Publications

• Koblizek V, Milenkovic B, Barczyk A, Tkacova R, Somfay A, Zykov K, Tudoric N, Kostov K, Zbozinkova Z, Svancara J, Sorli J, Krams A, Miravitlles M, Valipour A. Phenotypes of COPD patients with a smoking history in Central and Eastern Europe: the POPE Study. Eur Respir J. 2017 May 11;49(5):1601446. doi: 10.1183/13993003.01446-2016. Print 2017 May. PMID 28495687
• Bestall JC, Paul EA, Garrod R, Garnham R, Jones PW, Wedzicha JA. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999 Jul;54(7):581-6. doi: 10.1136/thx.54.7.581. PMID 10377201
• Karim A, Muhammad T, Shahid Iqbal M, Qaisar R. A multistrain probiotic improves handgrip strength and functional capacity in patients with COPD: A randomized controlled trial. Arch Gerontol Geriatr. 2022 Sep-Oct;102:104721. doi: 10.1016/j.archger.2022.104721. Epub 2022 May 10. PMID 35567889
• Su Z, Ma C, Ru X, Zhang S, Wu C, Huang Y, Cen H, Yin Z, Zhang J. Effects of probiotic treatment on patients and animals with chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized control trials. Front Cell Infect Microbiol. 2024 Sep 11;14:1411222. doi: 10.3389/fcimb.2024.1411222. eCollection 2024. PMID 39324058
• Patibandla S, Bhatt N, Lief S, Beauti SM, Ansari AZ. Gut Microbiota Modulation in the Management of Chronic Obstructive Pulmonary Disease: A Literature Review. Cureus. 2024 Aug 14;16(8):e66875. doi: 10.7759/cureus.66875. eCollection 2024 Aug. PMID 39280360
• Panahi Y, Ghanei M, Vahedi E, Mousavi SH, Imani S, Sahebkar A. Efficacy of probiotic supplementation on quality of life and pulmonary symptoms due to sulfur mustard exposure: a randomized double-blind placebo-controlled trial. Drug Chem Toxicol. 2017 Jan;40(1):24-29. doi: 10.3109/01480545.2016.1166250. Epub 2016 Apr 14. PMID 27079636
• Aghamohammadi M, Ghodrati S, Jalili N, Jafari R, Rafiee E, Kamali K, Ghasemi M, Alizargar J. Effects of the oral probiotic Familact on dyspnea management in COPD patients: A randomized controlled trial. Heart Lung. 2025 May-Jun;71:63-68. doi: 10.1016/j.hrtlng.2025.02.002. Epub 2025 Feb 27. PMID 40020522
• Ertan Yazar E, Niksarlioglu EY, Yigitbas B, Bayraktaroglu M. How to Utilize CAT and mMRC Scores to Assess Symptom Status of Patients with COPD in Clinical Practice? Medeni Med J. 2022 Jun 23;37(2):173-179. doi: 10.4274/MMJ.galenos.2022.06787. PMID 35735170

Identifiers

NCT: NCT07339280 · UHS-COPD-PROBIO-2025 · 2181-147/01-06/LJ.Z.-25-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗