Bronchoscopy for Mucus Removal in Asthma

(FOCUS Trial)

Overseen By John Fahy, MD, MS

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Academic

Sponsor: University of California, San Francisco

Must not be taking: Anticoagulants

Disqualifiers: Smoking, Cystic fibrosis, COPD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and comfort of using bronchoscopy (a small camera tube) to remove mucus plugs from the airways of people with asthma. Researchers will also study the mucus to better understand its features. The trial seeks participants with asthma who have confirmed mucus plugs in their lungs, identifiable on a CT scan (a special type of X-ray). Those struggling with asthma and diagnosed with mucus plugs in their lungs might find this trial suitable. As an unphased trial, it offers a unique opportunity to contribute to scientific understanding and potentially improve asthma treatments.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using anticoagulant medications.

What prior data suggests that this protocol is safe for mucus removal in asthma patients?

Research has shown that bronchoscopy, a procedure to examine the lungs, is generally safe for individuals without asthma. However, specific safety data on using bronchoscopy to remove mucus plugs in people with asthma remains limited. One study suggested that bronchoscopy might aid in severe asthma cases. This indicates potential benefits, but safety details continue to be researched.

Medical procedures like this undergo close monitoring to ensure maximum safety. Researchers carefully observe study participants for any issues. If concerns arise, discussing them with a doctor or the study team is crucial. They can provide more information tailored to individual health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about therapeutic bronchoscopy for mucus removal in asthma because it offers a direct and immediate way to clear mucus plugs from the airways. Unlike standard treatments such as inhalers and corticosteroids that work by reducing inflammation and relaxing muscles around the airways, bronchoscopy physically removes the blockage. This procedure could provide rapid relief for patients whose mucus plugs are not effectively managed by current medications, potentially improving breathing and reducing asthma symptoms more quickly than traditional methods.

What evidence suggests that this protocol is effective for mucus removal in asthma?

Research shows that mucus plugs can block airways in people with asthma, leading to serious health problems. In severe cases, these plugs can cause suffocation by preventing air from reaching the lungs. Studies have found that removing these plugs can improve lung function. A clear connection exists between having fewer mucus plugs and achieving better results on breathing tests. In this trial, participants will undergo therapeutic bronchoscopy to remove mucus plugs, which may help asthma patients breathe more easily. ^{3 6 7 8 9}

Who Is on the Research Team?

John Fahy, MD, MS

Principal Investigator

Professor of Medicine

Are You a Good Fit for This Trial?

The FOCUS trial is for adults aged 18-80 with asthma, who have a CT mucus plug score over 5 and lung function (FEV1) below 80% but above 35% of the predicted value. Participants must not have other lung conditions like COPD or recent infections, no COVID-19 in the past month, no smoking recently or heavy smoking history, and can't be on blood thinners.

Inclusion Criteria

CT mucus plug score > 5.

Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

Pre-bronchodilator FEV1 < 80% predicted and ≥ 35% predicted

Exclusion Criteria

I have not had a cold or similar illness in the last 6 weeks.

I have had a cold or similar illness in the last month.

I have had COVID-19 in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Bronchoscopic removal of airway mucus plugs in patients with asthma

1 week

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Therapeutic bronchoscopy for removal of mucus plugs

Trial Overview This study tests how safe and tolerable it is to remove mucus plugs from the airways using bronchoscopy in asthma patients. It's conducted at one center and will also analyze characteristics of the removed mucus plugs.

How Is the Trial Designed?

Group I: Therapeutic bronchoscopy for removal of mucus plugs Experimental Treatment 1 Intervention

Protocol A: This protocol will study 10 patients with asthma who have CT (Computed Tomography) evidence of mucus plugs in their airways. Screening data will be reviewed to determine participant eligibility. Participants who meet all eligibility criteria will participate in a bronchoscopy done on one lung for the first 5 participants, and if single lung mucus removal is well tolerated then we will perform bronchoscopies on both lungs for the next 5 participants.

Therapeutic bronchoscopy for removal of mucus plugs is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Therapeutic bronchoscopy for:

• Central airway obstruction
• Foreign body aspiration
• Massive bleeding in the airways
• Asthma with mucus plugs

Approved in United States as Therapeutic bronchoscopy for:

• Central airway obstruction
• Foreign body aspiration
• Massive bleeding in the airways
• Asthma with mucus plugs

Approved in Canada as Therapeutic bronchoscopy for:

• Central airway obstruction
• Foreign body aspiration
• Massive bleeding in the airways
• Asthma with mucus plugs

Approved in Japan as Therapeutic bronchoscopy for:

• Central airway obstruction
• Foreign body aspiration
• Massive bleeding in the airways
• Asthma with mucus plugs

Approved in China as Therapeutic bronchoscopy for:

• Central airway obstruction
• Foreign body aspiration
• Massive bleeding in the airways
• Asthma with mucus plugs

Approved in Switzerland as Therapeutic bronchoscopy for:

• Central airway obstruction
• Foreign body aspiration
• Massive bleeding in the airways
• Asthma with mucus plugs

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study of 73 asthmatic children experiencing 187 episodes of mucus plugging, it was found that this condition often occurred during severe asthma attacks, particularly affecting multiple lung lobes, with the right lung being the most commonly involved.

Chest physiotherapy was identified as a beneficial treatment for mucus plugging in these children, while bronchoscopy was deemed unnecessary for managing this complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The problem of mucus plugging in children with asthma. Maxwell, GM.[2019]

In a respiratory emergency caused by mucus plugging, increasing the positive end-expiratory pressure (PEEP) on the ventilator led to immediate improvements in patient oxygenation and imaging results.

This case highlights a potential alternative intervention for managing respiratory failure due to mucus plugs, especially in rural hospitals where emergent bronchoscopy may not be readily available.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saved by the PEEP: Resolution of Complete Unilateral Lung Collapse Secondary to Mucus Plugging With Ventilator Technique. Ogbuka, I., Avera, S., Ivonye, C., et al.[2022]

Massive bronchopulmonary lavage is proposed as an effective treatment for severe chronic obstructive pulmonary diseases, focusing on the removal of retained mucus and foreign materials in the lungs.

The therapy involves bronchoscopic procedures performed by otolaryngologists, highlighting the importance of specialized skills in effectively addressing obstructive pulmonary conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchopulmonary levage to remove pulmonary casts and plugs. Passy, V., Ermshar, C.[2019]

Therapeutic bronchoscopy has evolved to include advanced minimally invasive techniques for managing serious lung conditions such as lung cancer, chronic obstructive pulmonary disease (COPD), and asthma.

New techniques discussed include bronchoscopic lung volume reduction, bronchial thermoplasty, radiofrequency ablation, and the use of fiducial markers for improving the precision of external beam radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in therapeutic bronchoscopy. Thakkar, MS., von Groote-Bidlingmaier, F., Bolliger, CT.[2018]

In cases of severe status asthmaticus, standard treatment may not be sufficient, and uncommon interventions like therapeutic bronchoscopy can lead to significant improvements in patients on mechanical ventilation.

The abstract presents two specific cases where therapeutic bronchoscopy was performed, highlighting its potential role in managing life-threatening asthma episodes, although its overall effectiveness in such situations remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchoscopy as a rescue therapy in patients with status asthmaticus: Two case reports and review of literature. Khan, MF., Al Otair, HA., Elgishy, AF., et al.[2021]

In a study of 126 patients with moderate to severe asthma, those with mucus plugging (MP) showed significantly worse lung function, indicated by lower FEV1% and FEV1/FVC ratios, suggesting that mucus plugging contributes to more severe airway obstruction.

Patients with MP also had higher levels of type 2 inflammation markers, such as blood eosinophils and total IgE, and experienced more frequent severe asthma exacerbations, indicating a strong association between mucus plugging and poorly controlled asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Associations of Mucus Plugging in Moderate to Severe Asthma. Chan, R., Duraikannu, C., Lipworth, B.[2023]

In a case study of an intubated adult female patient with severe asthma exacerbation unresponsive to standard treatments, the use of rhDNase after bronchoalveolar lavage led to significant improvement.

This suggests that rhDNase may be an effective intervention for managing mucus plugging in adults with refractory asthma, a condition that has been less studied compared to similar cases in children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nebulised DNase post-therapeutic bronchoalveolar lavage in near fatal asthma exacerbation in an adult patient refractory to conventional treatment. Chia, AC., Menzies, D., McKeon, DJ.[2021]

Bronchoscopy is a crucial diagnostic and therapeutic tool for respiratory diseases, particularly effective in treating conditions like hemoptysis and airway stenoses.

Recent advancements in endoscopic techniques, such as electrocautery and stent implantation, have expanded treatment options for patients with chronic obstructive pulmonary disease and uncontrolled asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interventional pulmonology procedures: an update. Gompelmann, D., Eberhardt, R., Herth, FJ.[2013]

A patient with asthma experienced acute respiratory distress due to atelectasis (lung collapse) in the right middle and lower lobes, which improved within 24 hours after treatment with intravenous steroids, inhalation therapy, and pulmonary physiotherapy.

The case highlights the importance of chest imaging in atypical asthma presentations and emphasizes that pulmonary physiotherapy and bronchodilators are crucial in treating atelectasis caused by mucous plugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transient marked atelectasis: an unusual complication of asthma in pregnancy. Onyeije, CI., Sherer, DM., Ham, L., et al.[2019]

Mucus plugs in asthma patients not only block airways but also contribute to ongoing inflammation, making them a significant factor in asthma symptoms like wheezing and shortness of breath.

Current asthma treatments may not address the issues caused by mucus plugs, which can lead to infections and exacerbate the disease, highlighting the need for new strategies to manage mucus in asthma care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Pathology of Asthma: What Is Obstructing Our View? Aegerter, H., Lambrecht, BN.[2023]

Citations

1. atsjournals.org atsjournals.org/doi/full/10.1164/rccm.202406-1244ED

Breaking up Mucus Plugs in Asthma Mucus plugs lead to bad outcomes in asthma. In fatal asthma, mucus plugs occlude airways, blocking gas exchange to cause asphyxia and death (1, ...

2. withpower.com withpower.com/trial/phase-asthma-2022-b65fe

Bronchoscopy for Mucus Removal in Asthma (FOCUS Trial) This is a single-center study that will evaluate the safety and tolerability of removal of mucus plugs by bronchoscopy in patients with asthma.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9851493/

Mucus Plugs Persist in Asthma, and Changes ... We found that the change in mucus plug score was negatively and significantly correlated with changes in FEV 1 % predicted.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1323893025000838

From mucus plugging to airway dilatation in chronic ... The findings indicate that dynamic alterations in airway mucus plugs may affect the risk of lung function decline and exacerbations in patients ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05748912/lung-function-outcomes-following-removal-of-airway-mucus-plugs-in-patients-with-asthma-focus

Lung Function Outcomes Following Removal of Airway ... This is a single-center study that will evaluate the safety and tolerability of removal of mucus plugs by bronchoscopy in patients with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4279340/

Is there a role for therapeutic bronchoscopy in acute severe ... Provided clinical expertise, bronchoscopy is considered safe in ventilated non-asthmatic patients.[1,2] At present, however, data regarding outcomes and safety ...

7. ctv.veeva.com ctv.veeva.com/study/lung-function-outcomes-following-removal-of-airway-mucus-plugs-in-patients-with-asthma-focus

Lung Function Outcomes Following Removal of Airway Mucus ... This is a single-center study that will evaluate the safety and tolerability of removal of mucus plugs by bronchoscopy in patients with asthma.

8. jaci-inpractice.org jaci-inpractice.org/article/S2213-2198(25)00066-2/fulltext

Mucus Plugging as a Prognostic Indicator for Biologic ... It has been demonstrated that patients with higher mucus scores exhibit worse pulmonary function, greater type 2 (T2) inflammation, and more frequent severe ...

9. atsjournals.org atsjournals.org/doi/10.1164/rccm.200704-571OC

Safety and Efficacy of Bronchial Thermoplasty in ... Measurements and Main Results: BT resulted in a transient worsening of asthma symptoms. Seven hospitalizations for respiratory symptoms occurred ...