Mini Bronchoalveolar Lavage for Lung Injury

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: WilliamJanssen

Disqualifiers: Transplantation, Hemoptysis, Bleeding risk, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The goal of this observational clinical trial is to learn about the role white blood cells (macrophages) play in lung inflammation in people with Acute Respiratory Distress Syndrome (ARDS). The main questions it aims to answer are: 1. How does the immune system respond to different kinds of lung injury and inflammation and how do those processes differ from each other? 2. What roles do the cells that live in the lungs (macrophages) play in turning off inflammation? How does their role differ from other cells that are called to the lung to help repair injury (recruited macrophages)? 3. Will more frequent testing of lung cell samples help reduce the time it takes to start treatment for ventilator-associated pneumonia (VAP) and therefore reduce the rates of initial therapy failure? Participants will be in the intensive care unit (ICU) on a mechanical ventilator (machine that helps patients breathe) because they have ARDS or are on a mechanical ventilator for some other reason (control group). The following will happen: 1. Participants will be given 100% oxygen through the breathing machine (mechanical ventilator) for 3-5 minutes. This is called pre-oxygenation. 2. A lung specialist (pulmonologist), a member of Dr. Janssen's research team, or respiratory therapist will place small amount of saline into the lung using a long catheter going through the breathing tube. 3. The fluid will be removed with suction and will be sent to the laboratory for testing. 4. This will be repeated two more times over the course of 10 days, or less if participants are taken off of the ventilator. The procedure will be performed no more than three times. 5. Two nasal brushings will be taken from the participants' nose. 6. Approximately 3 tablespoons of blood will be removed by putting a needle into the participants vein. This is the standard method used to obtain blood for tests. A total of 9 tablespoons will be taken for research purposes over the course of this study 7. Data including the participants age, sex, severity of illness, and other medical conditions will be recorded to determine how these can affect the white blood cells. 8. If bacteria are isolated from the fluid in the participants lung, the participants' physician may choose to place the participants on antibiotics to treat an infection. 9. A follow-up phone call may be made by a member of the research team after discharge from the hospital. At this time, the participant may be invited to participate in the Post-ICU clinic at National Jewish Health.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the research team or your doctor.

What data supports the effectiveness of the treatment Non-Bronchoscopic Mini Bronchoalveolar Lavage?

Non-bronchoscopic bronchoalveolar lavage (NB-BAL) has been shown to be a valuable method for obtaining lung samples in children with small airways, providing clinically significant information in 85% of cases without needing more invasive procedures. This suggests that NB-BAL can effectively gather important lung information, which may help in managing lung conditions. ^{1 2 3 4 5}

Is Mini Bronchoalveolar Lavage safe for humans?

Non-bronchoscopic bronchoalveolar lavage (NB-BAL) has been studied for safety in various groups, including preterm neonates and critically ill children. While generally considered safe, there can be potential effects on breathing and blood flow, especially in patients on mechanical ventilation. ^{2 5 6 7 8}

How does the mini bronchoalveolar lavage treatment differ from other treatments for lung injury?

Mini bronchoalveolar lavage is unique because it is a non-invasive procedure that uses a sterile, disposable feeding tube to collect lung fluid samples in mechanically ventilated infants, providing a safer and less costly alternative to traditional bronchoscopy, which is not feasible in small infants due to their small airways. ^{1 2 4 9 10}

Research Team

Eligibility Criteria

This trial is for ICU patients on mechanical ventilation due to ARDS or similar conditions, expected to remain ventilated for at least 48 hours. It's not suitable for those with chronic lung diseases, recent immunosuppressant use, history of organ transplant, severe bleeding risks, a directive against life-sustaining treatment, morbid state with less than 14 days survival expectancy or pregnancy.

Inclusion Criteria

I have given, or my legal representative has given, written consent for the study.

I am between 18 and 85 years old.

I have been admitted to the intensive care unit.

Exclusion Criteria

At significant risk for bleeding (INR > 3 or PTT > 3x normal)

Presence of pneumomediastinum or pneumothorax on recent imaging

Presence of an advanced directive with Do Not Intubate (DNI) status (Do Not Resuscitate (DNR) is acceptable)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Observation

Participants undergo procedures to collect lung fluid and nasal brushings for analysis of macrophage activity and bacterial presence.

10 days

3 procedures (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the observational procedures, including a potential follow-up phone call.

2-4 weeks

Treatment Details

Interventions

• Non-Bronchoscopic Mini Bronchoalveolar Lavage (Other)

Trial Overview The study observes how white blood cells in the lungs respond to inflammation from ARDS. Participants undergo non-bronchoscopic mini bronchoalveolar lavage (miniBAL) where saline is introduced and then removed from the lungs via a catheter for analysis. This helps understand immune responses and may expedite pneumonia treatment initiation.

Participant Groups

Group I: Study Population Group Experimental Treatment 1 Intervention

People in the ICU on mechanical ventilation due to a diagnosis of ARDS or any other diagnosis that requires mechanical ventilation (following surgery, sepsis without lung involvement, seizures)

Who Is Running the Clinical Trial?

WilliamJanssen

Lead Sponsor

Trials

1

Recruited

60+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Dr. Gary H. Gibbons

National Heart, Lung, and Blood Institute (NHLBI)

Chief Executive Officer since 2012

MD from Harvard Medical School

Dr. James P. Kiley

National Heart, Lung, and Blood Institute (NHLBI)

Chief Medical Officer since 2011

MD from University of California, San Francisco

Findings from Research

Saline instillation followed by suctioning in healthy piglets significantly increased the opening pressures of the lungs, indicating a change in lung mechanics that could affect ventilation.

Despite a significant decrease in arterial oxygen levels after the procedure, the values remained within the high normal range, suggesting that while there are effects on lung function, they may be manageable with appropriate recruitment maneuvers and PEEP (positive end-expiratory pressure).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inflation lung mechanics deteriorates markedly after saline instillation and open endotracheal suctioning in mechanically ventilated healthy piglets. Cunha-Goncalves, D., Perez-de-Sá, V., Ingimarsson, J., et al.[2015]

Non-bronchoscopic bronchoalveolar lavage (NB-BAL) is generally safe and well-tolerated in critically ill mechanically ventilated children, with only 7% experiencing significant immediate complications that required increased support.

While there was no overall significant change in oxygenation index (OI) after the procedure, some patients did experience temporary increases in OI, particularly those with baseline OIs greater than 20, indicating the need for careful monitoring in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How safe is non-bronchoscopic bronchoalveolar lavage in critically ill mechanically ventilated children? Burmester, M., Mok, Q.[2020]

A new method using a 4F balloon wedge pressure catheter allows for bronchoalveolar lavage (BAL) in children with small artificial airways, making it possible to sample alveolar contents without needing a larger bronchoscope.

In a study of 20 children aged 1 month to 6.5 years, this nonbronchoscopic BAL technique successfully provided valuable clinical information in 85% of cases, avoiding the need for open lung biopsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonbronchoscopic approach to bronchoalveolar lavage in children with artificial airways. Alpert, BE., O'Sullivan, BP., Panitch, HB.[2019]

This study is the first to provide data on bronchoalveolar lavage in healthy South African children, revealing that alveolar macrophages are the main cell type present, while those with inflammatory lung conditions showed increased neutrophils.

Exogenous pulmonary surfactant exposure significantly reduced inflammatory cytokines and increased anti-inflammatory cytokines (IL-10 and IL-12), suggesting that surfactant treatment could be beneficial in reducing inflammation in respiratory diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exogenous surfactant on Paediatric Bronchoalveolar lavage derived macrophages' cytokine secretion. van Rensburg, L., van Zyl, JM., Smith, J., et al.[2020]

Nonbronchoscopic bronchoalveolar lavage (NB-BAL) is a safe procedure for diagnosing ventilator-associated pneumonia (VAP) in preterm neonates, with only minor transient complications observed in 19.5% of cases and no significant adverse effects on respiratory or cardiopulmonary function.

In a study of 31 neonates, NB-BAL successfully diagnosed VAP in 69.6% of cases, allowing for targeted antibiotic treatment in over half of the patients, highlighting its clinical utility in the NICU.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical application of nonbronchoscopic bronchoalveolar lavage in preterm neonates with clinical ventilator-associated pneumonia. Liao, CC., Tsai, MH., Lai, SH., et al.[2021]

In a study involving 20 mechanically ventilated patients, the paediatric bronchoscope provided similar bronchoalveolar lavage yields compared to the adult bronchoscope, indicating it is equally effective for this procedure.

The use of the paediatric bronchoscope resulted in significantly lower respiratory and haemodynamic side effects, such as less increase in intratracheal pressure and systemic arterial pressures, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult and paediatric size bronchoscopes for bronchoalveolar lavage in mechanically ventilated patients: yield and side effects. Ricou, B., Grandin, S., Nicod, L., et al.[2019]

In a study involving 14 patients with acute lung injury or ARDS, nonbronchoscopic lavage was found to cause less significant changes in heart rate and blood pressure compared to bronchoscopic lavage, suggesting it may be a safer option for certain patients.

Bronchoscopic lavage resulted in a greater reduction in minute ventilation and an increase in carbon dioxide levels compared to nonbronchoscopic lavage, indicating that nonbronchoscopic methods may be less physiologically stressful.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of nonbronchoscopic lavage in ARDS. Perkins, GD., Chatterjee, S., Giles, S., et al.[2022]

Bronchoalveolar lavage (BAL) significantly reduced the need for invasive mechanical ventilation in neonates with severe pneumonia, with only 30% requiring it after BAL compared to 70% at admission.

Patients in the BAL group experienced shorter hospital stays (9.2 days) and lower hospital costs (12,557 Yuan) compared to the control group (14.1 days and 19,121 Yuan), with no significant adverse side effects observed during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Bronchoalveolar Lavage as Adjunct Therapy in the Treatment of Neonatal Severe Pneumonia: A Prospective Case-Control Study. Liu, J., Zhao, HR., Wei, HL., et al.[2021]

This study provides the first reference values for bronchoalveolar lavage (BAL) in 'normal' Greek children, showing that alveolar macrophages are the predominant cell type in healthy lungs.

In children with inflammatory lung diseases, BAL fluid showed significantly higher levels of neutrophils and cytokines like IL-8 and TNF-alpha, suggesting these measurements could be useful for early detection of lung inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bronchoalveolar lavage in children with inflammatory and non inflammatory lung disease. Gidaris, D., Kanakoudi-Tsakalidou, F., Papakosta, D., et al.[2021]

A new nonbronchoscopic bronchoalveolar lavage technique using a sterile feeding tube was successfully performed on 15 intubated infants, allowing for effective diagnosis of pulmonary infections without the complications associated with traditional bronchoscopy.

This method resulted in a specific diagnosis for 60% of the patients and showed radiographic improvement in two cases, demonstrating its safety and clinical utility in treating respiratory failure in small infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonbronchoscopic bronchoalveolar lavage in mechanically ventilated infants: technique, efficacy, and applications. Koumbourlis, AC., Kurland, G.[2019]

References

1. United States pubmed.ncbi.nlm.nih.gov

Inflation lung mechanics deteriorates markedly after saline instillation and open endotracheal suctioning in mechanically ventilated healthy piglets. [2015]

2. United States pubmed.ncbi.nlm.nih.gov

How safe is non-bronchoscopic bronchoalveolar lavage in critically ill mechanically ventilated children? [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Nonbronchoscopic approach to bronchoalveolar lavage in children with artificial airways. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Effect of exogenous surfactant on Paediatric Bronchoalveolar lavage derived macrophages' cytokine secretion. [2020]

5. Singapore pubmed.ncbi.nlm.nih.gov

Safety and clinical application of nonbronchoscopic bronchoalveolar lavage in preterm neonates with clinical ventilator-associated pneumonia. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Adult and paediatric size bronchoscopes for bronchoalveolar lavage in mechanically ventilated patients: yield and side effects. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Safety and tolerability of nonbronchoscopic lavage in ARDS. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Efficacy of Bronchoalveolar Lavage as Adjunct Therapy in the Treatment of Neonatal Severe Pneumonia: A Prospective Case-Control Study. [2021]

9. Greece pubmed.ncbi.nlm.nih.gov

Bronchoalveolar lavage in children with inflammatory and non inflammatory lung disease. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Nonbronchoscopic bronchoalveolar lavage in mechanically ventilated infants: technique, efficacy, and applications. [2019]