Gerard Criner, MD, FACP, FACCP, outlines the details of the SPRAY-CB clinical trial for the treatment of chronic bronchitis in patients with COPD.
Hello. My name is jerry Criner. I'm professor and founding chair department of forensic medicine and surgery at the louis Katz School of Medicine at Temple University. I'm going to describe to you a new trial for chronic bronchitis called spray CB, which is metered dose nitrogen cryo spray for treatment of chronic bronchitis. In patients with COPD, these are my disclosures I received research monies that went to my institution for conduct of studies with C. S. A. Medical as well as consultant fees for study design. Let's talk about the importance of chronic bronchitis. Well, chronic bronchitis first is defined as the presence of productive cough for three months and two successive years. Other causes of chronic cough should be excluded when associated with COPD patients with chronic bronchitis experience worse lung function, impaired health status, reduce exercise tolerance more frequent and more severe exacerbations and increased mortality. 11 looks at the prevalence of chronic bronchitis in the United States. In a national health interview survey conducted in 2011, approximately 10 million americans reported a diagnosis of chronic bronchitis and a prevalence rate of chronic bronchitis went across race, gender and age. However, about 70% of those cases occurred in patients that were 45 years of age or greater so highly prevalent disease. In the population of the United States, the presence of chronic bronchitis also appears to relate to the prevalence of the severity of airflow obstruction In this study by Montes de Oca and colleagues in a latino study, 60% of patients who had gold, Grade II or higher airflow obstruction had a diagnosis of chronic bronchitis. Again, this slide outlines where the risk for chronic bronchitis. Primary risk is smoking. The cumulative 30 year incidence of chronic bronchitis and current smokers is about 42% of those having chronic bronchitis. Occupational risk are also important exposures. The biomass fuels dust and chemical fumes guard maybe the causative um ideology. In some cases gender predisposition is variable and other factors may predispose to chronic bronchitis, like childhood infections, presence of bronchi emphasis in about 4 to 22% of never smokers. These are some data on the occupational burden of chronic bronchitis. In this study which included 2000 U. S. Residents who completed a telephone interview scoring to respiratory health and occupational history. Self exposure to vapors, dust, gas or fumes. During the longest held job was recorded And passive occupational exposures significantly increase the likelihood of chronic obstructive pulmonary disease independent of smoking effects. And as you can see in this study, approximately 15-29% of patients had chronic bronchitis were exposed to vapors, dust or fumes. This slide shows the causes of excess mucus and COPD. It could be related to the left side of the slide, increased production of mucus by inflammatory cells, Oxidative stress, viral infection or bacterial infection could prime goblet cells to express more mucus production or it could be on the opposite uh decrease the limitation elimination. Shown on the right side of the slide due to poor celery clearance airway occlusion, reduce excretory muscle force and respiratory muscle weakness. This looks at some morphology of the airway and patients with chronic bronchitis is data by seda and colleagues that looked at God would cell hyperplasia and epithelial inflammation and peripheral airways of smokers with chronic bronchitis and chronic airflow limitation. And as one can see the patients who were smokers compared to the non smokers had significant increase in the numbers of goblet cells, inflammatory cells, neutrophils, macrophages and um T cells. Now this like shows some of the implications of chronic bronchitis on quality of life. Looking at an overall quality of life with sF 36 were disease specific quality of life and patients with COPD to write with the SDR. Q. And these analysis include cohorts from the lovely smokers and COPD gene studies and have found that smokers with COPD without chronic airflow obstruction were younger and had greater BME and less smoke exposures than those with chronic airflow obstruction alone and equality of life scores were worse for those patients that chronic bronchitis only. Yeah. These days, I looked at the effect of chronic sputum production and respiratory symptoms in COPD using a daily electronic dialogue, agree in 50 outpatients with COPD and over 14,000 days of observation. Two thirds of these patients had significant daily speed and production and those patients with COPD who had greater complaints of speed and production had more respiratory symptoms in terms of cough and dysosmia. We's and nasal symptoms. The importance of having daily speed of production isn't only on daytime symptoms but also on nocturnal symptoms. Here. You can see a study by Hartman and colleagues showed that patients with frequent speed and production had more disturbed sleep. They were poorer sleepers. They had to sit during the night days, set up and cough. They had um more likely had only fair or poor quality of sleep and um used sleep medicines threefold uh greater incidents because of poor sleep called related to cough. So this slide highlights our current medical treatments with chronic bronchitis. You can see smoking cessation, physical measures, expectorant, short and long acting bronchodilators and held steroids, fossil disgrace inhibitors and anti oxidants have all been used, all with limited to no success. Currently, the treatment of chronic bronchitis is a significant unmet need in patients with COPD in an attempt to address this unmet need this study. Spray CB is a sham controlled prospective randomized clinical trial of the rejuvenation air system for the treatment of moderate to severe COPD that has chronic bronchitis. The primary endpoint of the study is a change in saint George respiratory questionnaire score from baseline to 12 months an improvement. Secondary endpoints are the number of subjects experienced one serious adverse event related to the study device or procedure within the first month after the first or second study period. A changing call from baseline through 12 months, measured objectively with the use of a cough meter reduction of speed and from baseline 3, 12 months reduction in the rate of exacerbation. All severity is over 12 months. And a change in a cat scare score or COPD assessment tests From baseline through 12 months. This slide shows the set up of the rejuvenation system to the left shows the power device that provides a delivered meter cry a spray based on lung anatomy of liquid nitrogen through a bronchus cope under direct visualization. And the system is designed to be automatic so that any pulmonologist with bronchoscopy skills could perform the therapy, not those who have elite skills who are interventional pulmonologist. Yeah. So the rejuvenation system is primed to have a standardized technique to provide reproducible results. A map is used to prime the delivery of sprays and the number of sprays and the meter dose sprays based individually on the patient's anatomy and a unique interface drives the standardized metered cryo spray that's specific to the individual patients volume of their airway. So this short video shows the delivery of the cross grey showing a ring of frost that can be seen on the tissue towards the end of the spray treatment. Yeah. Mhm. Mhm. You can see the starting to develop in a circumferential ring as the spray emanates in a 360° pattern around the tip of the Catheter. Yeah. Yeah. Okay. Yeah. Yeah. Yeah. Okay. Mhm. Yeah. Okay. Yeah spray CB study inclusion criteria include the following patient is able to sign informed consent has moderate or severe airflow obstruction. Gold two or 3 patient is being treated according to currently medically accepted treatment guidelines for chronic bronchitis for at least three months prior to the study and agrees to continue maintenance pulmonary respiratory medications through the duration of study, non smoking for a minimum of two months prior consent and agrees to continue non smoking for the duration of study and patient is able to undergo to bronchoscopy procedures per hospital governor exclusion criteria includes these recent respiratory infection, other origins of respiratory disease besides chronic bronchitis, current smoking any substance either cigarettes or e cigarettes or vaping life threatening arrhythmias, bullets. Emphysema of the large bullet greater than 30 millimeters. Significant clinical bronchi exorcist, solid organ transplant known mucosal terror, prior lung surgeries such as Newman, ectomy, lumpectomy, bull ectomy or lung volume reduction surgery within the last one year. Other exclusion criteria is the patient has had other interventional treatments for emphysema. Can't uh cease the temporary use of an anticoagulant therapy, unstable non pulmonary disease is expected to affect the outcome in the next six months to a year. Subject is pregnant or planning to conceive receiving chemo or radiotherapy patient is in another clinical trial or patient has known sensitivity and medications used during a bronchoscopy procedure is an overall scheme of spray CB study design. Um There's a patients get consent. Have a two week run in period where they use a daily diary to record their symptoms, eligible patients who are compliant more than 60% of the time or randomized 2 to 1 to either receive treatment with spray CB Or sham control treatment patients are then followed sequentially over a 12-month period of time. Those randomized sham control if they meet eligibility at that point or allowed to cross over to active treatment arm multiple study procedures are done to assess patients outcome over that period. So in summary chronic bronchitis is very common in smokers and those with COPD. It is associated with an accelerated decline in lung function. Greater risk of acute exacerbation, worst respiratory symptoms and overall greater mortality. Current treatment options beyond bronchodilators and inhaled steroids are limited better therapies, such as illustrated here by a spray CB that are currently being studied that may directly target chronic bronchitis, improved symptoms and alter the risk of exacerbation are needed and hopefully will help to fill this void. If you have a patient that you think might be eligible for this trial, please contact us either at the email or phone number provided below or happy to talk to you at any time. If you need any other information for your patients