Supported by Asthmatx, Inc. Alair and Asthmatx are registered trademarks of Asthmatx, Inc. Advair is a registered trademark of GlaxoSmithKline, Inc. Symbicort is a registered trademark of AstraZeneca, Inc.

1. Introduction:
Asthma is a serious public health problem. The current estimate is that 20 million people in the United States suffer from asthma. Each year in the United States alone, there are approximately 13.6 million unscheduled physician office visits, 1.8 million emergency room visits, 0.5 million hospitalizations, and 4,000 deaths (NCHS 2005) due to asthma. The estimated annual cost of asthma in the United States is approximately $19.7 billion. This total includes $5 billion in indirect costs, due to more than 14.5 million lost work days, and $14.7 billion in direct costs, such as asthma medications, unscheduled physician office visits, emergency room visits and hospitalizations (American Lung Association 2007).
Ten percent of the more than 20 million Americans with asthma are diagnosed as having severe asthma. This group of severe asthmatics, however, is responsible for a disproportionate share of the morbidity associated with the disease. Thus, this 10% of patients with the most severe asthma are responsible for the majority of asthma-related healthcare burden, represented by the costs of hospitalizations, ER visits, physician office visits, and use of medications (Cisternas et al, 2003)
Despite regular treatment with high doses of available asthma medications, patients with severe asthma experience frequent and serious symptoms including exacerbations that may be life-threatening and require urgent resuscitative measures including intubation and mechanical ventilation, until the airway obstruction can be relieved. Exacerbations requiring medical intervention result in significant healthcare costs and affect the quality of life for the patient and family. This increased burden of severe asthma reflects the inability of the existing treatment options to adequately control asthma in patients with severe disease.
2. Case Presentation:
The typical patient is about 40 years old, has a history of poorly controlled severe asthma, and despite taking Advair, Symbicort or other equivalent combinations of ICS + LABA twice a day, still experiences difficulty in daily activities due to asthma symptoms.
Bronchial thermoplasty is typically administered in a hospital outpatient bronchoscopy or endoscopy suite or operating room. The patient should be stable to undergo bronchoscopy and the bronchoscopist needs to ensure that the patient remains a good candidate for bronchial thermoplasty by following the patient selection criteria outlined below. In some cases, the procedure may be safely performed on an in-patient basis where the patient can be monitored for a longer period of time before discharge. Patients who are described in the Precautions section 3.4 below might be such candidates.
3. Patient Selection:	
<ol>
<li>The Alair Bronchial Thermoplasty System is indicated for the treatment of severe persistent asthma in patients 18 years and older whose asthma is not well controlled with inhaled corticosteroids and long acting beta agonists.</li>
<li>Patients with the following conditions should not be treated:
<ul>
<li>Presence of a pacemaker, internal defibrillator, or other implantable electronic devices,</li>
<li>Known sensitivity to medications required to perform bronchoscopy, including lidocaine, atropine, and benzodiazepines,</li>
<li>Patients previously treated with the Alair System should not be retreated in the same area(s). No clinical data are available studying the safety and/or effectiveness of repeat treatments. </li></ul></li>
<li>Patients should not be treated while the following conditions are present:
<ul>
<li>Active respiratory infection,</li>
<li>Asthma exacerbation or changing dose of systemic corticosteroids for asthma (up or down) in the past 14 days,</li>
<li>Known coagulopathy,</li>
<li>As with other bronchoscopic procedures, patients should stop taking anticoagulants, antiplatelet agents, aspirin and NSAIDS before the procedure with physician guidance. </li></ul></li>
<li>Caution should be taken in patients with the following conditions due to a potential increased risk of adverse events that may be associated with the procedure. Patients with these conditions were not studied in the pivotal trial and the safety of Alair treatment for such patients has not been determined: 
<ul>
<li>Post-bronchodilator FEV1 &lt; 65%.</li>
<li>Other respiratory diseases including emphysema, vocal cord dysfunction, mechanical upper airway obstruction, cystic fibrosis or uncontrolled obstructive sleep apnea.</li>
<li>Use of short acting bronchodilator in excess of 12 puffs per day within 48 hours of bronchoscopy (excluding prophylactic use for exercise).</li>
<li>Use of oral corticosteroids in excess of 10 milligrams per day for asthma.</li>
<li>Increased risk for adverse events associated with bronchoscopy or anesthesia, such as pregnancy, insulin dependent diabetes, epilepsy or other significant co-morbidities, such as uncontrolled coronary artery disease, acute or chronic renal failure, and uncontrolled hypertension. The Alair System should only be used in patients stable enough to undergo bronchoscopy</li>
<li>Intubation for asthma, or ICU admission for asthma within the prior 24 months.</li>
<li>Any of the following within the past 12 months:
<ul>
<li>4 or more lower respiratory tract infections (LRTI)</li>
<li>3 or more hospitalizations for respiratory symptoms</li>
<li>4 or more OCS pulses for asthma exacerbation</li></ul></li></ul></li>
</ol>
4. 	Bronchial Thermoplasty Procedure:
<ol>
<li>On the day of the procedure, the bronchoscopist needs to reevaluate and ensure that the patient remains a good candidate for bronchial thermoplasty under moderate sedation.</li>
<li>Peri-procedure preparation includes prophylactic administration of OCS (50mg/d) for 3 days before, day of, and day after the procedure to minimize post procedure inflammation, and application of inhaled bronchodilators and anti-cholinergics to suppress airway secretions.</li>
<li>The patient is appropriately prepared and placed under moderate sedation. A peripheral intravenous (IV) line and supplemental oxygen (less than 40%) via oral or nasal cannula are recommended with appropriate monitoring for moderate sedation, which would include continuous electrical cardiac monitoring, continuous pulse oximetry, and noninvasive blood pressure monitoring. Once IV access is established and monitors have been applied, premedications can be administered to the patient in preparation for bronchial thermoplasty. Albuterol and an antisialogogue agent such as glycopyrrolate or atropine should be administered a minimum of 30 minutes before the procedure. Sedation administered is IV midazolam and fentanyl with judicious application of topical anesthesia.</li>
<li>Bronchial thermoplasty is performed using the Alair System. The equipment is prepared for use and a standard gel-type patient return electrode is affixed to the patient to provide a complete circuit.</li>
<li>Bronchial thermoplasty is performed with a standard commercially available high frequency compatible flexible bronchoscope either through an oral or nasal approach, and topical anesthesia applied accordingly. The bronchoscopist anesthetizes the posterior pharynx, vocal cords and bronchial tree before initiating treatment. As the bronchoscopist proceeds down the airways, additional local anesthetics are used as necessary.</li>
<li>The bronchoscope is navigated to the region of the lung to be treated and all target airways are inspected before treatment begins. The bronchoscopist plans the order in which the airway segments are to be accessed and treated, assisted by a map of the airways. Treatment planning is crucial to the thoroughness and ultimately to the success of BT, helping to avoid under- or overtreatment of the airways. </li>
<li>The bronchoscope is navigated to the first target treatment site, typically the most distal airway in the targeted lobe. The Alair Catheter is introduced through the working channel of the bronchoscope and positioned at the desired location in the airway. The electrode array at the tip of the Catheter is expanded to contact the airway wall and the bronchoscopist activates the RF Controller to deliver RF energy to the tissue.</li>
<li>The RF Controller delivers low-power, temperature-controlled RF energy to the airway, and automatically terminates the energy delivery upon completion of the cycle (approximately 10 seconds). A single activation of the Catheter delivers RF energy over a distance of approximately 5mm (the length of the exposed electrodes within the electrode array). The bronchoscopist must maintain static contact with the targeted 5 mm section during this time, even while airways remain in motion from tidal breathing.</li>
<li>The temperature set point, power limit, and delivery time are configured in the RF Controller software, and are not user adjustable.</li>
<li>Following the mapped treatment plan, the Catheter is deployed from the distal to the proximal end of the airway being treated. The Catheter is repositioned 5mm proximally after each activation and subsequent activations are performed contiguously avoiding overlap. This technique is used in all accessible airways distal to the mainstem bronchi and &ge; 3mm in diameter.</li>
<li>A systematic approach from distal to proximal, working methodically from airway to airway across the region of lung being treated is recommended to ensure that all accessible airways are carefully identified and treated only once. Depending on size and anatomy, a range of approximately 40-80 energy delivery cycles are performed.</li>
<li>BT is administered in 3 treatment sessions with a different region of the lung being treated during each session (one lower lobe in session 1; the second lower lobe in session 2; and both upper lobes in session 3). Each treatment is scheduled approximately 3 weeks apart. For the upper lobe regions (treated together typically in one treatment session), the procedure is identical to above, but requires additional time, as it involves navigating the tortuous anatomy of the upper airways and covers more area than either lower lobe. Depending on patient size and anatomy, a range of approximately 60-100 energy delivery cycles are performed.</li>
<li>The patient is followed in the recovery room until lung function returns to acceptable levels. This often takes up to 4 hours for each treatment session. See post-procedure follow up section for more details.</li>
</ol>
5. 	Post Procedure Follow Up:
<ol>
<li>Up to about 4-hour observation and recovery/monitoring period following each procedure.</li>
<li>Spirometry, breath sounds and vital signs (heart rate, blood pressure, temperature, respiratory rate, pulse oximetry) before discharge.</li>
<li>Discharge if Post-bronchodilator FEV1 is &ge; 80% of the pre-procedure value and patient is feeling well.</li>
<li>Verify prophylactic use of prednisone or equivalent the day following each bronchoscopy.</li>
<li>Contact patient via phone calls 1 day, 2 days and 7 days to assess post-procedure status.</li>
<li>Office visit at 2 to 3 weeks to assess pulmonary function and schedule subsequent bronchial thermoplasty procedures as appropriate.</li>
<li>Follow-up visits for long-term monitoring of improvement of asthma status as needed.</li>
</ol>
6. Outcome:
The Asthma Intervention Research 2 (AIR2) Trial evaluated the safety and effectiveness of the Alair Bronchial Thermoplasty System. The data from that study was submitted to the FDA and was the basis for the agency's approval of a novel device for the treatment of asthma. The AIR2 data was also published in the January 15, 2010 issue of the American Journal of Respiratory and Critical Care Medicine (AJRCCM). The trial demonstrated that treatment with the Alair System resulted in improved asthma quality of life, as well the following clinically significant benefits over sham during long-term follow-up: 
<ul>
<li>32 % reduction in asthma attacks</li>
<li>84 % reduction in emergency room visits for respiratory symptoms</li>
<li>73 %reduction in hospitalizations for respiratory symptoms </li>
<li>66 % reduction in days lost from work/school or other daily activities due to asthma </li>
</ul>


7. Conclusion:

Bronchial thermoplasty delivered by the Alair System provides a novel, procedure-based treatment for severe asthma that is refractory to conventional therapy. Pulmonologists, allergists, asthma experts, and respiratory therapists should become familiar with the use of bronchial thermoplasty and appropriate selection and management of patients for this procedure. Randomized, controlled clinical trials to date with bronchial thermoplasty have demonstrated 		significant improvement in outcomes that are important to our patients: quality of life, asthma symptoms, severe exacerbations requiring corticosteroids, days lost from work/school/other daily activities due to asthma, and healthcare utilization. Unlike the currently used drug therapies which require daily use to manage symptoms, bronchial thermoplasty provides benefits and improvements in overall asthma control that are long lasting.

<ol>
	<li>Castro, M., Musani, A., Mayse, M., Shargill, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bronchial+thermoplasty:+a+novel+technique+in+the+treatment+of+severe+asthma.">Bronchial thermoplasty: a novel technique in the treatment of severe asthma.</a> Ther Adv Respir Dis. 4 (2), 101-116 (2010).</li><li>Castro, M., Rubin, A. S., Laviolette, M., Fiterman, J., De Andrade, L. M., Shah, P. L., Fiss, E., Olivenstein, R., Thomson, N. C., Niven, R. M., Pavord, I. D., Simoff, M., Duhamel, D. R., McEvoy, C., Barbers, R., ten Hacken, N. H. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effectiveness+and+safety+of+Bronchial+Thermoplasty+in+the+treatment+of+severe+asthma:+a+multicenter,+randomized,+double-blind+sham-controlled+clinical+trial.">Effectiveness and safety of Bronchial Thermoplasty in the treatment of severe asthma: a multicenter, randomized, double-blind sham-controlled clinical trial.</a> Am J Respir Crit Care Med. 181, 116-124 (2010).</li><li>Cox, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bronchial+Thermoplasty.">Bronchial Thermoplasty.</a> Clin Chest Med. 31, 135-140 (2010).</li><li>Mayse, M. L., Laviolette, M., Rubin, A. S., Lampron, N., Simoff, M., Duhamel, D., Musani, A. L., Yung, R. C., Mehta, A. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+pearls+for+bronchial+thermoplasty.">Clinical pearls for bronchial thermoplasty.</a> J Bronchol. 14, 115-123 (2007).</li><li>Pavord, I. D., Cox, G., Thomson, N. C., Rubin, A. S., Corris, P. A., Niven, R. M., Chung, K. F., Laviolette, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Safety+and+efficacy+of+bronchial+thermoplasty+in+symptomatic,+severe+asthma.">Safety and efficacy of bronchial thermoplasty in symptomatic, severe asthma.</a> Am J Respir Crit Care Med. 176 (12), 1185-1191 (2007).</li><li>Cox, G., Thomson, N. C., Rubin, A. S., Niven, R. M., Corris, P. A., Siersted, H. C., Olivenstein, R., Pavord, I. D., McCormack, D., Chaudhuri, R., Miller, J. D., Laviolette, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Asthma+control+during+the+year+after+bronchial+thermoplasty.">Asthma control during the year after bronchial thermoplasty.</a> N Engl J Med. 356 (13), 1327-1337 (2007).</li><li>Wilson, S. R., Cox, G., Miller, J. D., Lam, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Global+assessment+after+bronchial+thermoplasty:+the+patient's+perspective.">Global assessment after bronchial thermoplasty: the patient's perspective.</a> Journal of Outcomes Research. 10, 37-46 (2007).</li><li>Cox, G., Miller, J. D., McWilliams, A., Fitzgerald, J. M., Lam, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Bronchial+thermoplasty+for+asthma.">Bronchial thermoplasty for asthma.</a> Am J Respir Crit Care Med. 173 (9), 965-969 (2006).</li><li>Brown, R. H., Wizeman, W., Danek, C., Mitzner, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effect+of+bronchial+thermoplasty+on+airway+distensibility.">Effect of bronchial thermoplasty on airway distensibility.</a> Eur Respir J. 26 (2), 277-282 (2005).</li><li>Brown, R. H., Wizeman, W., Danek, C., Mitzner, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=In+vivo+evaluation+of+the+effectiveness+of+bronchial+thermoplasty+with+computed+tomography.">In vivo evaluation of the effectiveness of bronchial thermoplasty with computed tomography.</a> J Appl Physiol. 98 (5), 1603-1606 (2005).</li><li>Miller, J. D., Cox, G., Vincic, L., Lombard, C. M., Loomas, B. E., Danek, C. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+prospective+feasibility+study+of+bronchial+thermoplasty+in+the+human+airway.">A prospective feasibility study of bronchial thermoplasty in the human airway.</a> Chest. 127 (6), 1999-2006 (2005).</li><li>Danek, C. J., Lombard, C. M., Dungworth, D., Cox, G., Miller, J. D., Biggs, M. J., Keast, T., Loomas, B. E., Wizeman, W. J., Hogg, J. C., Leff, A. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reduction+in+airway+hyperresponsiveness+to+methacholine+by+the+application+of+RF+energy+in+dogs.">Reduction in airway hyperresponsiveness to methacholine by the application of RF energy in dogs.</a> J Appl Physiol. 97, 1946-1953 (2004).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> National Center for Health Statistics (NCHS). , (2005).</li><li>Cisternas, M. G., Blanc, P. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+comprehensive+study+of+the+direct+and+indirect+costs+of+adult+asthma.">A comprehensive study of the direct and indirect costs of adult asthma.</a> J Allergy Clin Immunol. 111 (6), 1212-1218 (2003).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Trends in asthma morbidity and mortality. , (2007).</li></ol>

The authors were clinical investigators in the AIR2 Trial, the pivotal clinical study supporting the FDA approval of the Alair Bronchial Thermoplasty System.

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		<div>
		<table border="1">
		<thead>
		<tr>
		<th>Material Name</th>
		<th>Type</th>
		<th>Company</th>
		<th>Catalogue Number</th>
		<th>Comment</th>
		</tr>
		</thead>
		<tbody>
		
<tr>
<td>Standard diagnostic High Frequency Fiberoptic Bronchoscope</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>minimum 2.0 mm working channel</td>
</tr>
<tr>
<td>Alair Radio Frequency Controller</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Alair Bronchial Thermoplasty Catheter</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Gel Type Patient Return Electrode</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Continuous vital signs monitoring</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>heart rate, blood pressure, temperature, respiratory rate, pulse oximetry</td>
</tr>
<tr>
<td>Local Anesthetic: Lidocaine 1-2% (jelly and solution)</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Sedatives: Midazolam and Fentanyl</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Antiemetics: ondanestron or like</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Anticholinergic drying agent: Atropine or Glycopyrrolate</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Prednisone</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>3 days before, day of and day after procedure</td>
</tr>
<tr>
<td>Albuterol nebulizer</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Peripheral IV line</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Supplemental oxygen</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>less than 40% via oral or nasal cannula</td>
</tr>
<tr>
<td>Pulmonary Function Testing with Body Plethysmography</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<tr>
<td>Lung Map or procedure form for planning and recording of treatment</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>
<td>&nbsp;</td>		</tbody>
		</table>
		</div>

bronchial thermoplasty:  a novel therapeutic approach to severe asthma

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks. Bronchial thermoplasty is delivered by the Alair System and is performed in three outpatient procedure visits, each scheduled approximately three weeks apart. The first procedure treats the airways of the right lower lobe, the second treats the airways of the left lower lobe and the third and final procedure treats the airways in both upper lobes. After all three procedures are performed the bronchial thermoplasty treatment is complete.
Bronchial thermoplasty is performed during bronchoscopy with the patient under moderate sedation. All accessible airways distal to the mainstem bronchi between 3 and 10 mm in diameter, with the exception of the right middle lobe, are treated under bronchoscopic visualization. Contiguous and non-overlapping activations of the device are used, moving from distal to proximal along the length of the airway, and systematically from airway to airway as described previously. Although conceptually straightforward, the actual execution of bronchial thermoplasty is quite intricate and procedural duration for the treatment of a single lobe is often substantially longer than encountered during routine bronchoscopy. As such, bronchial thermoplasty should be considered a complex interventional bronchoscopy and is intended for the experienced bronchoscopist. Optimal patient management is critical in any such complex and longer duration bronchoscopic procedure. This article discusses the importance of careful patient selection, patient preparation, patient management, procedure duration, postoperative care and follow-up to ensure that bronchial thermoplasty is performed safely.
Bronchial thermoplasty is expected to complement asthma maintenance medications by providing long-lasting asthma control and improving asthma-related quality of life of patients with severe asthma. In addition, bronchial thermoplasty has been demonstrated to reduce severe exacerbations (asthma attacks) emergency rooms visits for respiratory symptoms, and time lost from work, school and other daily activities due to asthma.

Watch this Scientific Journal Video about Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma at JoVE.com

Bronchial Thermoplasty:  A Novel Therapeutic Approach to Severe Asthma

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled manner to reduce excessive airway smooth muscle. Reducing airway smooth muscle decreases the ability of the airways to constrict, thereby reducing the frequency of asthma attacks.

Bronchial thermoplasty is a non-drug procedure for severe persistent asthma that delivers thermal energy to the airway wall in a precisely controlled ...

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Vascular Occlusion Training for Inclusion Body Myositis: A Novel Therapeutic Approach

Inclusion body myositis (IBM) is a rare idiopathic inflammatory myopathy. It is known to produces remarkable muscle weakness and to greatly compromise function and quality of life. Moreover, clinical practice suggests that, unlike other inflammatory myopathies, the majority of IBM patients are not responsive to treatment with immunosuppressive or immunomodulatory drugs to counteract disease progression1. Additionally, conventional resistance training programs have been proven ineffective in restoring muscle function and muscle mass in these patients2,3. Nevertheless, we have recently observed that restricting muscle blood flow using tourniquet cuffs in association with moderate intensity resistance training in an IBM patient produced a significant gain in muscle mass and function, along with substantial benefits in quality of life4. Thus, a new non-pharmacological approach for IBM patients has been proposed. Herein, we describe the details of a proposed protocol for vascular occlusion associated with a resistance training program for this population.

The present article presents the details pertaining to the application of resistance training associated to vascular occlusion in IBM patients.

Inclusion body myositis (IBM) is a rare idiopathic inflammatory myopathy. It is known to produces remarkable muscle weakness and to greatly compromise ...

A Novel Surgical Approach for Intratracheal Administration of Bioactive Agents in a Fetal Mouse Model

Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide the basis for new therapeutic strategies for a variety of genetic and acquired diseases. Apart from congenital or inherited abnormalities with the requirement for long-term expression of the delivered gene, several non-inherited perinatal conditions, where short-term gene expression or pharmacological intervention is sufficient to achieve therapeutic effects, are considered as potential future indications for this kind of approach. Candidate diseases for the application of short-term prenatal therapy could be the transient neonatal deficiency of surfactant protein B causing neonatal respiratory distress syndrome1,2 or hyperoxic injuries of the neonatal lung3. Candidate diseases for permanent therapeutic correction are Cystic Fibrosis (CF)4, genetic variants of surfactant deficiencies5 and &alpha;1-antitrypsin deficiency6.
Generally, an important advantage of prenatal gene therapy is the ability to start therapeutic intervention early in development, at or even prior to clinical manifestations in the patient, thus preventing irreparable damage to the individual. In addition, fetal organs have an increased cell proliferation rate as compared to adult organs, which could allow a more efficient gene or stem cell transfer into the fetus. Furthermore, in utero gene delivery is performed when the individual's immune system is not completely mature. Therefore, transplantation of heterologous cells or supplementation of a non-functional or absent protein with a correct version should not cause immune sensitization to the cell, vector or transgene product, which has recently been proven to be the case with both cellular and genetic therapies7.
In the present study, we investigated the potential to directly target the fetal trachea in a mouse model. This procedure is in use in larger animal models such as rabbits and sheep8, and even in a clinical setting9, but has to date not been performed before in a mouse model. When studying the potential of fetal gene therapy for genetic diseases such as CF, the mouse model is very useful as a first proof-of-concept because of the wide availability of different transgenic mouse strains, the well documented embryogenesis and fetal development, less stringent ethical regulations, short gestation and the large litter size.
Different access routes have been described to target the fetal rodent lung, including intra-amniotic injection10-12, (ultrasound-guided) intrapulmonary injection13,14 and intravenous administration into the yolk sac vessels15,16 or umbilical vein17. Our novel surgical procedure enables researchers to inject the agent of choice directly into the fetal mouse trachea which allows for a more efficient delivery to the airways than existing techniques18.

We developed a novel surgical approach for intratracheal administration of bioactive agents into the mouse fetus. The delivery route is more efficient in targeting the fetal mouse lungs than the commonly used intra-amniotic injection. This procedure has to date not been described in a mouse model.

Prenatal pulmonary delivery of cells, genes or pharmacologic agents could provide the basis for new therapeutic strategies for a variety of genetic and ...

A Contusion Model of Severe Spinal Cord Injury in Rats

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is described to obtain a consistent model of severe SCI. Use of a stereotactic frame and computer controlled impactor allows for creation of reproducible injury. Hypothermia and urinary tract infection pose significant challenges in the post-operative period. Careful monitoring of animals with daily weight recording and bladder expression allows for early detection of post-operative complications. The functional results of this contusion model are equivalent to transection models. The contusion model can be utilized to evaluate the efficacy of both neuroprotective and neuroregenerative approaches.

A contusion model of severe spinal cord injury is described. Detailed pre-operative, operative and post-operative steps are described to obtain a consistent model.

The translational potential of novel treatments should be investigated in severe spinal cord injury (SCI) contusion models. A detailed methodology is ...

The Goeckerman Regimen for the Treatment of Moderate to Severe Psoriasis

Psoriasis is a chronic, immune-mediated inflammatory skin disease affecting approximately 2-3% of the population. The Goeckerman regimen consists of exposure to ultraviolet B (UVB) light and application of crude coal tar (CCT). Goeckerman therapy is extremely effective and relatively safe for the treatment of psoriasis and for improving a patient's quality of life. In the following article, we present our protocol for the Goeckerman therapy that is utilized specifically at the University of California, San Francisco. This protocol details the preparation of supplies, administration of phototherapy and application of topical tar. This protocol also describes how to assess the patient daily, monitor for adverse effects (including pruritus and burning), and adjust the treatment based on the patient's response. Though it is one of the oldest therapies available for psoriasis, there is an absence of any published videos demonstrating the process in detail. The video is beneficial for healthcare providers who want to administer the therapy, for trainees who want to learn more about the process, and for prospective patients who want to undergo treatment for their cutaneous disease.

Psoriasis is a chronic, immune-mediated inflammatory skin disease. The Goeckerman regimen, formulated for the treatment of psoriasis, consists of exposure to ultraviolet B (UVB) light and application of crude coal tar (CCT). The following protocol is for the administration of Goeckerman therapy for the treatment of moderate-to-severe psoriasis.

Psoriasis is a  chronic, immune-mediated inflammatory skin disease affecting approximately 2-3%  of the population. The Goeckerman regimen consists of ...

A Novel Approach for the Administration of Medications and Fluids in Emergency Scenarios and Settings

The available routes of administration commonly used for medications and fluids in the acute care setting are generally limited to oral, intravenous, or intraosseous routes, but in many patients, particularly in the emergency or critical care settings, these routes are often unavailable or time-consuming to access. A novel device is now available that offers an easy route for administration of medications or fluids via rectal mucosal absorption (also referred to as proctoclysis in the case of fluid administration and subsequent absorption). Although originally intended for the palliative care market, the utility of this device in the emergency setting has recently been described. Specifically, reports of patients being treated for dehydration, alcohol withdrawal, vomiting, fever, myocardial infarction, hyperthyroidism, and cardiac arrest have shown success with administration of a wide variety of medications or fluids (including water, aspirin, lorazepam, ondansetron, acetaminophen, methimazole, and buspirone). Device placement is straightforward, and based on the observation of expected effects from the medication administrations, absorption is rapid. The rapidity of absorption kinetics are further demonstrated in a recent report of the measurement of phenobarbital pharmacokinetics. We describe here the placement and use of this device, and demonstrate methods of pharmacokinetic measurements of medications administered by this method.

This study presents a novel device that offers an easy route to quickly provide medications and fluids in patients with limited or difficult IV access. This small-diameter device is placed in the distal third of the rectum, allowing for ongoing medication and fluids administration.

The available routes of administration commonly used for medications and fluids in the acute care setting are generally limited to oral, intravenous, or ...

A Component-resolved Diagnostic Approach for a Study on Grass Pollen Allergens in Chinese Southerners with Allergic Rhinitis and/or Asthma

Sensitization to grass pollen imposes a global risk for allergic airway diseases. Although prevention relies on local investigation of the pollen allergens, data on this topic are limited in southern China. Any available data were obtained by self-report questionnaires, skin prick tests, and total or specific IgE tests using crude extracts. For many reasons, these methods are unreliable. Serum sIgE reactivity to Bermuda grass, Timothy grass, and Humulus scandens allergens in a cohort of patients from Greater Guangzhou (southern China&#39;s largest city and its outskirts) with allergic rhinitis and/or asthma were examined using a fully-automated immunoassay analyzer as a component-resolved diagnostics (CRD) tool.
For the first time, a considerably high prevalence of Bermuda grass sIgE positivity was demonstrated in Chinese southerners with allergic rhinitis and/or asthma. In these patients, a subtle prevalence of sensitization to Timothy grass and Humulus scandens was also noted, which may arise from cross-reactivity, as the latter two are not common in the region. This was also supported by the detection of allergen components.
Fully-automated immunoassay analyzers may offer satisfactory consistency between regions, laboratories, and institutions and over time. The automaticity of the instrument may enable a standardized detection that would not have been readily revealed before the advent of CRD.
This is a study that uses a CRD approach to investigate sensitization to grass pollen allergens in southern China. It adds to current evidence in the literature. Future studies are needed to validate these findings. However, although CRD is a useful tool, the findings made with the fully-automated immunoassay analyzer should not substitute for other laboratory investigations, clinical evaluations, and physician expertise.

This work describes a protocol that uses a component-resolved approach to study sensitization to grass pollen allergens in a cohort of patients from southern China with allergic rhinitis and/or asthma.

Sensitization to grass pollen imposes a global risk for allergic airway diseases. Although prevention relies on local investigation of the pollen ...

Cardiopulmonary Bypass in a Mouse Model: A Novel Approach

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization and for minimizing organ damage resulting from prolonged extracorporal circulation. The goal of this paper was to demonstrate a fully functional and clinically relevant model of cardiopulmonary bypass in a mouse. We report on the device design, perfusion circuit optimization, and microsurgical techniques. This model is an acute model, which is not compatible with survival due to the need for multiple blood drawings. Because of the range of tools available for mice (e.g., markers, knockouts, etc.), this model will facilitate investigation into the molecular mechanisms of organ damage and the effect of cardiopulmonary bypass in relation to other comorbidities.

This paper describes how to perform cardiopulmonary bypass in mice. This novel model will facilitate the investigation of the molecular mechanisms involved in organ damage.

As prolonged cardiopulmonary bypass becomes more essential during cardiac interventions, an increasing clinical demand arises for procedure optimization ...

A Novel Approach to Overcome Movement Artifact When Using a Laser Speckle Contrast Imaging System for Alternating Speeds of Blood Microcirculation

The laser speckle contrast imager (LSCI) provides a powerful yet simple technique for measuring microcirculatory blood flow. Ideal for blood dynamic responses, the LSCI is used in the same way as a conventional Laser Doppler Imager (LDI). However, with a maximum skin depth of approximately 1 mm, the LSCI is designed to focus on mainly superficial blood flow. It is used to measure skin surface areas of up to 15 cm x 20 cm. The new technique introduced in this paper accounts for alternating speeds of microcirculations; i.e. both slow and fast flow flux measurement using the LSCI. The novel technique also overcomes LSCI&#39;s biggest shortcoming, which is high sensitivity to artifact movement. An adhesive opaque patch (AOP) is introduced for satisfactory recording of microcirculatory blood flow, by subtracting the LSCI signal from the AOP from the laser speckle skin signal. The optimal setting is also defined because the LSCI is most powerful when flux changes are measured relative to a reference baseline, with blood microcirculatory flux expressed as a percentage change from the baseline. These changes may be used for analyzing the status of the blood flow system.

This study introduces a novel technique for the measurement and analysis of alternating speeds of blood microcirculation in a single experiment using a laser speckle contrast imager.

The laser speckle contrast imager (LSCI) provides a powerful yet simple technique for measuring microcirculatory blood flow. Ideal for blood dynamic ...

Severe Burn Injury in a Swine Model for Clinical Dressing Assessment

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological pathways impair the inflammation response, resulting in delayed wound healing. Impaired wound healing frequently occurs in patients with diabetes leading to unfavorable outcomes such as amputation. Hence, dressings having beneficial effect in promoting burn wound repair are needed. However, studies on burn wound treatment are limited due to lack of proper animal models. Our previous study demonstrated wound-healing performance in rat and swine models using a minimally invasive surgical technique. This study aimed to demonstrate a swine model of severe burn injury that eliminates wound contraction and more closely approximates the human processes of re-epithelialization and new tissue formation. This protocol provides a detailed procedure for creating consistent burn wounds and examining the wound-healing performance under the treatment of an experimental dressing in a swine model. Six burn wounds were created symmetrically on the dorsum, which were covered with a clinical dressing composed of four layers: an inner contact layer of experimental materials, an inner intermediate layer of waterproof film, an outer intermediate layer of gauze, and an outer layer of adhesive plaster. Upon the completion of experiments, wound closure, wound area, and Vancouver Scar Scale score were examined. The samples of skin resected from each animal post-sacrifice were histologically prepared and stained using hematoxylin and eosin staining. Antibacterial activity of each dressing in the context of wound healing was also examined. The application of the clinical dressing to the wounds in swine model mimics the biological processes of human wound healing with respect to the processes of epithelialization, cellular proliferation, and angiogenesis. Therefore, this swine model provides an easy-to-learn, cost-effective, and robust method to assess the effect of clinical dressings in severe burn injury.

To closely mimic the mode of burn injuries requires the interplay between clinical observation and studies in animal models. In this study, a swine model of severe burn injury was established to assess an experimental dressing in physiological and pathophysiological settings.

Wound healing is a dynamic repair process and is the most complex biological process in human life. In response to burn injury, alterations in biological ...

A Novel Approach to Monitoring Graft Neovascularization in the Human Gingiva

Laser speckle contrast imaging (LSCI) is a novel method for measuring superficial blood perfusion over large areas. Since it is non-invasive and avoids direct contact with the measured area, it is suitable for monitoring blood flow changes during wound healing in human patients. Vestibuloplasty is periodontal surgery to the oral vestibule, aiming to restore vestibular depth with simultaneous enlargement of the keratinized gingiva. In this special clinical case, a split thickness flap was elevated at the first upper premolar and a xenogenic collagen matrix was adapted to the resulting recipient bed. LSCI was used to monitor the re- and neovascularization of the graft and the surrounding mucosa for one year. A protocol is introduced for the correct adjustment of microcirculation measurement in the oral mucosa, highlighting difficulties and possible failures.
The clinical case study presented demonstrated that &#8212; following the appropriate protocol &#8212; LSCI is a suitable and reliable method for following up microcirculation in a healing wound in the human oral mucosa and gives useful information on graft integration.

This study introduces a protocol for measuring microcirculation in human oral mucosa by laser speckle contrast imaging. The monitoring of wound healing after vestibuloplasty combined with a xenogenic collagen graft is presented on a clinical case.

Laser speckle contrast imaging (LSCI) is a novel method for measuring superficial blood perfusion over large areas. Since it is non-invasive and avoids ...