Bronchial Thermoplasty: New Treatment for Severe Asthma
Bronchial thermoplasty is a minimally invasive treatment regimen for severely asthmatic patients. A complete treatment includes three separate bronchoscopic procedures performed in an outpatient suite under conscious sedation, with no hospitalization required. In each procedure, which takes about one hour, a catheter within an expandable wire basket makes contact with airway walls and delivers about 10 seconds of thermal energy per actuation. The number of regions treated varies depending on the patient’s lung size, but the intent is to treat every visible airway 3 mm in diameter or greater. We start treatment at the farthest distal region of the airway and work backward (proximal) to the main bronchi.
Each lower lobe is treated in its own session and then both upper lobes are treated in a third session to complete the treatment. In anticipation of Food and Drug Administration approval in 2010, we are building a clinical program in the Respiratory Institute that incorporates bronchial thermoplasty into our existing comprehensive Asthma Center as a treatment option for individuals who would likely benefit from the procedure.
Eosinophilic Esophagitis: Utility of Allergy Immunology Evaluation
In recent years, eosinophilic esophagitis (EoE) has emerged as a condition encountered more frequently by allergy/immunology and gastroenterology specialists. In patients with EoE, esophageal symptoms occur in association with an eosinophil-rich infiltrate in the esophagus, defined as > 15 eosinophils per high-power field in the appropriate clinical context.
The etiology, appropriate management and natural history of EoE are poorly understood. At Cleveland Clinic, we recently carried out a study to assess the utility of routine allergy/immunology evaluation in adults with EoE.
Consensus-Based Recommendations for Management
The high rate of allergic rhinitis, atopic dermatitis and asthma reported in case series of pediatric and adult EoE patients, combined with the established role of eosinophils in atopic disease, imply that, at least in some patients, immunoglobulin E (IgE)-mediated or IgE-associated response to one or more antigens may provoke and perpetuate this inflammatory disorder.
Recent consensus-based recommendations for EoE management state that patients should undergo allergy/immunology evaluation; however, these recommendations are based primarily on pediatric studies. Although immediate hypersensitivity skin testing has been associated with excellent negative predictive value and can reliably detect clinically relevant inhalant and/or food allergens in individuals with IgE-mediated disorders, the value of skin (or in vitro) testing has not been established in adult patients with EoE.
Cleveland Clinic Experience
In a study carried out at Cleveland Clinic involving 26 subjects with EoE (confirmed by history and upper gastrointestinal endoscopy with biopsy and referred for allergy/immunology evaluation), 13 (50 percent) exhibited wheal/flare reaction to > 1 food. Of the 15 subjects with EoE who had concomitant respiratory symptoms, 14 (93 percent) had wheal/flare reaction to one or more inhalants. Twenty-one of these 26 subjects (81 percent) had > 1 allergen identified, 16 (62 percent) had > 5 allergens identified and 4 (15 percent) had > 10 allergens identified (range: 0 to 20 allergens identified). Peanut, egg, soy, cow’s milk and tree nuts (including walnut, almond and Brazil nut) were the most common food allergens identified in our series. Allergy/immunology evaluation frequently leads to detection of allergens via skin (or in vitro) testing that can direct avoidance measures.3 In patients with EoE, avoidance measures carry the potential for improving outcomes by reducing both symptoms and reliance on medication. These findings provide further support for the utility of routine allergy/immunology evaluation for adults with EoE.
- Penfield JD, Lang D, Goldblum JR, Falk GW. The role of allergy evaluation in adults with eosinophilic esophagitis. J Clin Gastroenterology. 2010 Jan;44(1):22-27.
- Furuta GT, Liacouras CA, Collins MH, et al. Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology. 2007 Oct;133(4):1342-1363.
- Bernstein IL, Li JT, Bernstein DI, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008 Mar;100 (3 Suppl):S1-S148.
Identifying and Validating Exhaled Breath Biomarkers for Detecting Early-Stage Lung Cancer
Our group’s current research is aimed at identifying and validating exhaled breath biomarkers for lung cancer. To date, studies that have evaluated exhaled breath volatile organic compound (VOC) profiles in lung cancer patients have used various mass spectrometry technologies and chemical sensor matrices to find a unique lung cancer signal in the exhaled breath.
We have been fortunate to bring two advanced sensing technologies to our breath biomarker research group. The first is called a single photon ionization mass spectrometer (SPIMS). A major benefit of this system is the ability to detect VOCs at an order of magnitude lower in concentration than previously available devices (down to the level of parts per trillion to parts per quadrillion), and to do so in near-real time (other devices require one-hour analysis times for the processing of breath). We have one of only two SPIMS systems in the world (the other is with the environmental Protection Agency). The second technology we are studying is a colorimetric sensor array (COSAT).
This disposable cartridge is impregnated with compounds that change their color upon exposure to VOCs. The output from the sensor is the pattern of color changes seen on the array. Our team’s next step is to analyze the breath of patients with early-stage lung cancer and compare the breath VOCs to those from patients at risk of developing lung cancer. We hope this work will move us closer to our goal of developing a breath test that can accurately screen for, and diagnose, lung cancer in a noninvasive manner.
Compassionate Use of Mepolizumab for Treating Life-Threatening HES
At Cleveland Clinic, we have recently been able to offer access to mepolizumab (recombinant anti-interleukin-5 monoclonal antibody) to subjects with life-threatening hypereosinophilic syndrome (HES) through a compassionate-use, open-label study. The study subjects’ disease could not be adequately controlled with steroid or other steroid-sparing therapies.
HES is a heterogeneous multisystem disorder characterized by persistent peripheral blood eosinophilia and end-organ involvement by eosinophils. Classically, it has been defined as having prolonged peripheral eosinophilia of > 1.5 E9 cells/L for at least six months, with no evidence of other recognized causes of eosinophilia and with evidence of target-organ damage.
The goal of HES therapy is to control peripheral blood and tissue eosinophilia and prevent irreversible organ damage and thromboembolic events associated with uncontrolled eosinophilia. First-line therapy usually includes systemic steroids for HES in general or imatinib mesylate in patients with documented myeloproliferative variant HES. Steroid therapy, however, typically does not induce a complete remission, and prolonged steroid therapy with its attendant toxicity usually is required for long-term management of HES patients.
Mepolizumab is given via monthly IV infusions and binds to serum interleukin-5 (IL-5) with high affinity and specificity, preventing it from binding to the L-5 receptor on the surface of eosinophils. Recent publications have suggested mepolizumab’s efficacy in investigational use in subjects with asthma, eosinophilic gastrointestinal disorders and HES, and it may be efficacious as a steroid-sparing agent and as a primary therapy to prevent organ damage.
Our own experience suggests that this product is well tolerated with minimal drug-related toxicity, and is effective in controlling peripheral blood eosinophilia and modulating target-organ damage in subjects with steroid-sensitive disease.