<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_3010"
                     title="Allergy Shots Cut Asthma but Carry Risk (CME/CE)"
                     score="-0.002"
                     href="http://www.medpagetoday.com/AllergyImmunology/Asthma/tb/21676?impressionId=1283456788648"
                     
      &lt;p&gt;Asthma patients need less medication and show reductions in symptoms following allergy desensitization treatment, though local and systemic reactions appear relatively common, an updated Cochrane review found.&lt;/p&gt;
&lt;p&gt;In a meta-analysis of 88 trials of several different kinds of allergy immunotherapies in asthma patients, Michael Abramson, MD, of Monash University in Melbourne, Australia, and colleagues found that treating only three to four patients would prevent one from having a symptom flare.&lt;/p&gt;
&lt;p&gt;Pooled data from placebo-controlled studies that reported effects on asthma symptom scores, covering 727 patients receiving allergy desensitization and 557 assigned to placebo, showed a reduction in symptom severity of 0.59 points (95% CI 0.35 to 0.83) on a 20-point standardized scale.&lt;/p&gt;
&lt;p&gt;But in their report published online in the &lt;em&gt;Cochrane Database of Systematic Reviews&lt;/em&gt;  --  updating an earlier meta-analysis published in 1995  --  the researchers cautioned that the included studies varied substantially in methodology, and that treatment allocations may not have been concealed adequately in most of the 72 studies billed as double- or single-blind.&lt;/p&gt;
&lt;p&gt;Abramson and colleagues also noted that the numbers needed to harm for localized or systemic reactions to the immunotherapies were not a lot larger than the numbers needed to treat for efficacy endpoints.&lt;/p&gt;
&lt;p&gt;For every 16 patients treated, one localized reaction was noted. And systemic reactions such as hives or breathing difficulties occurred in one patient for every nine treated, although fatal anaphylaxis was extremely rare.&lt;/p&gt;
&lt;p&gt;&quot;The evidence assembled in this review confirms the efficacy of immunotherapy in terms of a reduction in asthma symptoms and use of asthma medication,&quot; Abramson and colleagues wrote.&lt;/p&gt;
&lt;p&gt;&quot;The data show that immunotherapy can be considered when asthma is extrinsic and an unavoidable clinically relevant allergen can be identified,&quot; they recommended.&lt;/p&gt;
&lt;p&gt;On the other hand, the limitations of the individual studies and the meta-analysis process meant that the degree of benefit could not be readily compared with other asthma therapies. Abramson and colleagues indicated that immunotherapy &quot;is possibly comparable to inhaled steroids,&quot; but it&apos;s equally possible that the benefit is much smaller.&lt;/p&gt;
&lt;p&gt;They also suggested that, in view of the risk of reactions, patients receiving allergen desensitizations be kept under observation long enough to detect and treat serious reactions.&lt;/p&gt;
&lt;p&gt;To be included in the meta-analysis, trials had to be randomized and controlled using some type of allergen-specific immunotherapy and reporting at least one clinical outcome related to asthma.&lt;/p&gt;
&lt;p&gt;Abramson and colleagues identified 88 that met these basic criteria. House mite allergens were used in 42 studies, pollen allergens in 27 trials, and animal dander proteins in 10. Other trials examined mold, latex, or multiple allergens.&lt;/p&gt;
&lt;p&gt;Nearly all the control treatments were placebo. Sixty-three of the trials were double-blind, nine were single-blind, 13 were open-label, and three had mixed or unclear designs.&lt;/p&gt;
&lt;p&gt;But the researchers determined that only 16 of the blinded studies had &quot;clearly adequate&quot; strategies to assure that participants did not know their treatment assignments.&lt;/p&gt;
&lt;p&gt;&quot;The adequacy or otherwise of 57 studies could not be determined from the details published in the papers ... and further information was sought from the authors, but rarely forthcoming,&quot; Abramson and colleagues remarked.&lt;/p&gt;
&lt;p&gt;Despite this limitation, all 88 trials were included in the pooled assessments.&lt;/p&gt;
&lt;p&gt;Twenty-one of these reported quantitative information on medication use. As with symptom scores, Abramson and colleagues pooled the data and reported the relative change between immunotherapy and control treatment on a 20-point standardized scale. They found that the interventions reduced medication use by a mean of 0.53 points (95% CI 0.27 to 0.80).&lt;/p&gt;
&lt;p&gt;When these trials were combined with 17 others that simply reported whether medication use increased, decreased, or stayed the same, Abramson and colleagues determined that treating five patients with immunotherapy (95% CI 4 to 7) would prevent one from needing an increase in medication.&lt;/p&gt;
&lt;p&gt;Wide variations in study methodologies precluded firm conclusions regarding lung function or airway sensitivity to irritant compounds, the researchers found.&lt;/p&gt;
&lt;p&gt;The pooled data indicated no significant effect on FEV&lt;sub&gt;1&lt;/sub&gt; values but some benefit on bronchial hyperreactivity (0.35-point reduction, 95% CI 0.11 to 0.59, from 18 studies). For the latter endpoint, Abramson and colleagues found that results varied significantly depending on the specific challenge agent used, such as methacholine versus histamine or cold air.&lt;/p&gt;
&lt;p&gt;The researchers recommended additional research in several areas, including clinical identification of patients most likely to respond to allergen desensitization and the allergens best targeted in asthma, as well as ways to reduce adverse reactions.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;No external funding for the work was received.&lt;/p&gt;&lt;p&gt;Abramson reported receiving a speaking fee in 2006 from Boehringer Ingelheim and a research grant from Reckitt Benckiser.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_2917"
                     title="HAE Drug Data See Peer-Reviewed Light of Day (CME/CE)"
                     score="-0.007"
                     href="http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/tb/21554?impressionId=1283456788648"
                     
      &lt;p&gt;Results of phase III trials of two approved drugs for hereditary angioedema (HAE) and another in the late-stage pipeline have finally emerged from the gauntlet of peer review.&lt;/p&gt;
&lt;p&gt;Reports on a pasteurized and nanofiltered form of human C1 esterase inhibitor (Cinryze) and the synthetic agents ecallantide (Kalbitor) and icatibant (Firazyr)  --  the latter still in development  --  appeared in the Aug. 4 issue of the &lt;em&gt;New England Journal of Medicine&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Much of the data in all three papers had already been reported at meetings in &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/AAAAI/8810&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/AAAAI/8810&quot; target=&quot;_blank&quot;&gt;2008&lt;/a&gt; and &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ACAAI/11703&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ACAAI/11703&quot; target=&quot;_blank&quot;&gt;2009&lt;/a&gt;, but this is the first publication of full reports in a peer-reviewed journal.&lt;/p&gt;
&lt;p&gt;HAE, a rare disorder, is the result of a genetic defect in a regulatory protein that keeps C1 complement in check. Patients suffer frequent, unpredictable attacks marked by swelling and acute pain in various parts of the body.&lt;/p&gt;
&lt;p&gt;The C1 esterase inhibitor Cinryze, as well as a similar agent (Berinert) already FDA approved for acute attacks, are straight replacement products, derived from human plasma and treated to eliminate viral contaminants. The synthetic drugs come at HAE a different way, targeting bradykinin activity to block the downstream inflammatory effects of overactive complement.&lt;/p&gt;
&lt;p&gt;Icatibant is an antagonist of the bradykinin B2 receptor, whereas ecallantide inhibits plasma kallikrein to reduce bradykinin availability. Both drugs are given by subcutaneous injection, whereas the C1 esterase inhibitor proteins require intravenous delivery.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Icatibant Trials Disappointing&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;Aleena Banerji, MD, of Massachusetts General Hospital in Boston, and colleagues reported data from two phase III trials of icatibant, FAST-1 and FAST-2. The results explain why the FDA in 2008 rejected a marketing application submitted by its manufacturer, the German firm Jerini AG.&lt;/p&gt;
&lt;p&gt;Paradoxically, the placebo-controlled FAST-1 trial failed to meet its primary endpoint, a significant reduction in median time to clinically significant relief of acute HAE attacks, whereas FAST-2 did show a significant advantage versus an active comparator.&lt;/p&gt;
&lt;p&gt;In the 56-patient FAST-1 study, the median time to meaningful symptom relief was 2.5 hours compared with 4.6 hours in the placebo group (&lt;em&gt;P&lt;/em&gt;=0.14).&lt;/p&gt;
&lt;p&gt;In FAST-2, a similar effect was seen for icatibant, but patients receiving the active comparator, tranexamic acid, had far worse outcomes than the placebo patients in FAST-1. Median response times in FAST-2 were 2.0 hours for icatibant versus 12.0 hours with tranexamic acid (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;Differences between the two studies in the use of rescue medications likely accounted for the different outcomes, Banerji and colleagues indicated, not any action of tranexamic acid.&lt;/p&gt;
&lt;p&gt;Nearly half the placebo group in FAST-1 required rescue medication with C1 esterase inhibitor or other treatments because of inadequate relief or worsening symptoms. In FAST-2, on the other hand, only about 20% of patients assigned to tranexamic acid received rescue medications.&lt;/p&gt;
&lt;p&gt;Data from patients receiving rescue medication were not censored. Also, the primary endpoint in FAST-1 was judged only for the &quot;index symptom,&quot; the patient&apos;s primary complaint at the start of treatment, and not for other symptoms.&lt;/p&gt;
&lt;p&gt;This &quot;stringent definition&quot; of the primary endpoint and inclusion of placebo patients who received early rescue medication explained the relatively small difference in outcomes in FAST-1, Banerji and colleagues concluded.&lt;/p&gt;
&lt;p&gt;Nevertheless, Jerini is now sponsoring another trial, FAST-3, in hopes of allaying the FDA&apos;s doubts about the drug&apos;s efficacy.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Ecallantide Report Has No Mention of Anaphylaxis&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;The ecallantide report, from Marco Cicardi, MD, of the University of Milan, and colleagues, covered the drug&apos;s 72-patient, placebo-controlled pivotal trial called EDEMA3 in patients with acute attacks.&lt;/p&gt;
&lt;p&gt;Median time to significant improvement  --  defined as the patient&apos;s first report that overall symptoms were &quot;a lot better or resolved&quot;  --  was 2.75 hours with ecallantide compared with more than four hours for placebo.&lt;/p&gt;
&lt;p&gt;That was not the study&apos;s primary endpoint, however, which was a so-called treatment outcome score at four hours after treatment. Scores could range from -100 to +100, reflecting significant worsening or significant improvement, respectively.&lt;/p&gt;
&lt;p&gt;The mean four-hour score was 46.8 (SD 59.3) with ecallantide versus 21.3 (SD 69) in the placebo group (&lt;em&gt;P&lt;/em&gt;=0.004), Cicardi and colleagues reported.&lt;/p&gt;
&lt;p&gt;The report sidestepped mention of hypersensitivity or anaphylactic reactions that have &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/AAAAI/18843&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/AAAAI/18843&quot; target=&quot;_blank&quot;&gt;previously been reported&lt;/a&gt; with the drug. Cicardi and colleagues indicated that no such reactions occurred in EDEMA3.&lt;/p&gt;
&lt;p&gt;But a total of 16 such reactions had been seen in other trials, leading the FDA to require a boxed warning indicating that the drug should be administered by health professionals prepared to manage serious reactions.&lt;/p&gt;
&lt;p&gt;The problem has dashed hopes, at least for the present, that patients could carry ecallantide self-injectors to treat acute HAE attacks themselves.&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Cinryze Looking for Acute Tx Indication&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;The piece of the &lt;em&gt;NEJM&lt;/em&gt; package included a report from Bruce Zuraw, MD, of the University of California San Diego, and colleagues on the nanofiltered C1 esterase inhibitor Cinryze. It covered two studies, a 68-patient placebo-controlled trial of the drug as a treatment for acute attacks, and a 22-patient study of twice-weekly Cinryze treatments for preventing attacks.&lt;/p&gt;
&lt;p&gt;Cinryze won FDA approval in October 2008 for preventing HAE attacks, and the &lt;em&gt;NEJM&lt;/em&gt; report includes data from a trial for that purpose. But its manufacturer is also seeking approval for the drug as a treatment for acute attacks; data from a study intended to support that indication were also included in the &lt;em&gt;NEJM&lt;/em&gt; paper&lt;/p&gt;
&lt;p&gt;The acute-attack trial had time to &quot;unequivocal&quot; symptom relief as its primary outcome. The median was 2.0 hours for Cinryze versus more than 4.0 hours for placebo (&lt;em&gt;P&lt;/em&gt;=0.02), according to Zuraw and colleagues.&lt;/p&gt;
&lt;p&gt;On the other hand, 40% of Cinryze patients failed to achieve unequivocal relief within four hours, the researchers indicated, a lower success rate than seen in earlier studies.&lt;/p&gt;
&lt;p&gt;Zuraw and colleagues also reported that open-label treatment resulted in improvement 93% of the time. They suggested this finding might be a better representation of real-life clinical responses, as &quot;fear of receiving placebo&quot; would not be a factor.&lt;/p&gt;
&lt;p&gt;Nevertheless, the FDA last year told the drug&apos;s manufacturer, ViroPharma, that &lt;a href=&quot;http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/14578&quot; mce_href=&quot;http://www.medpagetoday.com/Rheumatology/GeneralRheumatology/14578&quot; target=&quot;_blank&quot;&gt;another acute-treatment trial&lt;/a&gt; would be needed before approval for an acute-treatment indication would be granted. The agency indicated that the existing data &quot;lacked robustness,&quot; according to the company.&lt;/p&gt;
&lt;p&gt;Berinert was approved last year as a treatment for acute attacks, but Cinryze is currently the only drug approved for preventing them.&lt;/p&gt;
&lt;p&gt;The prophylaxis trial, which used a placebo-controlled crossover design, found that only two of the 22 patients had more HAE attacks during the 12-week active-treatment period relative to a 12-week placebo period.&lt;/p&gt;
&lt;p&gt;The mean number of attacks in the Cinryze group was 6.26, compared with 12.73 for placebo (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;&lt;strong&gt;Choosing One Agent Over Another&lt;/strong&gt;&lt;/p&gt;
&lt;p&gt;An accompanying editorial by B. Paul Morgan, MB, PhD, of Cardiff University in Wales, noted that clinicians now need studies to help them sort through the trade-offs involved with using one of these agents versus another.&lt;/p&gt;
&lt;p&gt;Noting that C1 esterase inhibitors have been marketed in Europe for many years, he wrote that this class &quot;has proved to be safe and effective during decades of use.&quot;&lt;/p&gt;
&lt;p&gt;But the other agents have advantages as well, he pointed out. &quot;Newer agents eliminate the perceived risk of infection; some provide additional target specificity,&quot; Morgan wrote.&lt;/p&gt;
&lt;p&gt;&quot;Head-to-head comparisons are needed to guide the choice of agents for the treatment of acute attacks and prophylaxis,&quot; according to Morgan. &quot;Practical matters, particularly the stability of the drug and the route of administration, are likely to be critical, because optimal therapy requires prompt self-administration at the first hint of an attack.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The C1 esterase inhibitor study was funded by Lev Pharmaceuticals, now owned by ViroPharma Biologics.&lt;/p&gt;&lt;p&gt;The ecallantide study was funded by Dyax.&lt;/p&gt;&lt;p&gt;The icatibant studies were funded by Jerini AG, now part of Shire, with partial National Institutes of Health support for FAST-1.&lt;/p&gt;&lt;p&gt;Zuraw reported consulting relationships with Lev, CSL Behring, Jerini, and Dyax; travel expenses from Lev, Shire, and Dyax; expert witness fees from Lev; and grant support from Lev, Shire, and Pharming. One co-author was an employee of Lev.&lt;/p&gt;&lt;p&gt;Cicardi reported consulting relationships with Dyax, Jerini, and Pharming; board membership at Jerini, Shire, and CSL Behring; travel reimbursements from Dyax, Jerini, Shire, CSL Behring, and Pharming; honoraria and speaking fees from Jerini, Shire, Pharming, CSL Behring, and ViroPharma; and manuscript preparation fees from Jerini. Two co-authors were Dyax employees.&lt;/p&gt;&lt;p&gt;Banerji reported consulting relationships with Shire and Dyax. Seven co-authors were Jerini employees.&lt;/p&gt;&lt;p&gt;Morgan reported giving expert testimony on behalf of Shire, with fees paid to his university.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_2865"
                     title="Social Rejection Linked to Inflammation (CME/CE)"
                     score="-0.007"
                     href="http://www.medpagetoday.com/Psychiatry/AnxietyStress/tb/21484?impressionId=1283456788648"
                     
      &lt;p&gt;Social rejection may be bad for your health  --  at least that&apos;s the implication of a small study linking rejection to increases in inflammatory markers associated with disorders such as asthma, arthritis, cardiovascular disease, and depression.&lt;/p&gt;
&lt;p&gt;The study, conducted in the lab among 124 healthy adults, found a test of social rejection triggered increases in oral levels of two inflammatory markers, Shelley Taylor, PhD, and colleagues at the University of California Los Angeles reported.&lt;/p&gt;
&lt;p&gt;Further testing in 31 of those participants found that one of the two inflammatory markers was associated with greater activity in brain regions linked to processing rejection-related distress, Taylor and colleagues wrote online in the &lt;em&gt;Proceedings of the National Academy of Sciences&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;While the study was small, the findings start to pin down the neural pathways that are involved in reactions to acute social stress and may help explain the &quot;considerable variability&quot; in susceptibility to disorders with an inflammatory component, the researchers argued.&lt;/p&gt;
&lt;p&gt;Taylor and colleagues conducted a two-part experiment  --  a standard stress test involving speaking and calculating under pressure in public and a functional magnetic resonance imaging study of brain regions active when participants were socially rejected.&lt;/p&gt;
&lt;p&gt;In the first, 124 healthy adult volunteers took the Trier Social Stress test, which involves composing and delivering an impromptu speech to a panel of nonresponsive judges. Then they were asked to perform difficult mental arithmetic  --  counting backward from 2,935 by 7s and by 13s  --  while being urged to go faster by an &quot;apparently exasperated experimenter,&quot; Taylor and colleagues wrote.&lt;/p&gt;
&lt;p&gt;Before and after the test, the researchers collected oral fluids, which were tested for levels of a soluble receptor for tumor necrosis factor-&amp;#945; (sTNF&amp;#945;RII) and interleukin-6 (IL-6), both known to be markers of inflammatory activity.&lt;/p&gt;
&lt;p&gt;As expected, Taylor and colleagues wrote, levels of both markers increased significantly, at&lt;em&gt; P&lt;/em&gt;&amp;lt;0.005 for sTNF&amp;#945;RII and &lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 for IL-6, and the increases were positively and significantly correlated (at r=0.53 and &lt;em&gt;P&lt;/em&gt;&amp;lt;0.001).&lt;/p&gt;
&lt;p&gt;The volunteers were asked to complete a second experiment  --  playing a computer game called Cyberball while undergoing fMRI scanning. All told, 31 participants were eligible and took part.&lt;/p&gt;
&lt;p&gt;In the game, participants had to throw a virtual ball back and forth to two other &quot;players&quot; but did not know that the other players were actually computer-generated. In one game, the ball was shared equally, but in the other, the volunteer got a few passes at the beginning and then was ignored for the rest of the 60-throw game.&lt;/p&gt;
&lt;p&gt;The researchers correlated levels of the two markers, as measured after the previous stress test, with activity in regions of the brain previously linked with rejection-related stress  --  the dorsal anterior cingulate cortex (dACC) and the anterior insula.&lt;/p&gt;
&lt;p&gt;As expected, Taylor and colleagues wrote, those who had high levels of sTNF&amp;#945;RII on the stress test had significantly elevated activity in both regions during the game in which they were excluded, as compared with the game in which they were included. The differences were significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.005 for the dACC and &lt;em&gt;P&lt;/em&gt;&amp;lt;0.05 for both the right and left anterior insula.&lt;/p&gt;
&lt;p&gt;On the other hand, the researchers reported, IL-6 was only weakly correlated with one region  --  the right anterior insula.&lt;/p&gt;
&lt;p&gt;&quot;Considered together,&quot; they argued, &quot;these data demonstrate that neural responses to social rejection are associated with potentiated inflammatory responses to an episode of acute social stress.&quot;&lt;/p&gt;
&lt;p&gt;Taylor and colleagues cautioned that the observed associations were correlational, so that causality can&apos;t be determined. As well, they said, more research is needed to see if neural responses to social rejection are uniquely related to differences in inflammatory responses or if they are part of a more general system that can be activated by several types of negative events.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by the NIH and a Society in Science: Branco Weiss Fellowship.&lt;/p&gt;&lt;p&gt;The authors declared they had no conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_1911"
                     title="ATS: Heat Device Maintains Asthma Control Long Term (CME/CE)"
                     score="-0.031"
                     href="http://www.medpagetoday.com/MeetingCoverage/ATS/tb/20258?impressionId=1283456788648"
                     
      NEW ORLEANS  --  Patients with moderate to severe asthma had symptomatic improvement for up to five years after treatment with a devices that uses radiofrequency energy to reduce airway smooth muscle mass, according to results reported here.&lt;br&gt;
&lt;br&gt;Prebronchodilator FEV&lt;sub&gt;1&lt;/sub&gt; averaged 70% of predicted at baseline and 70.6% five years after a single treatment with bronchial thermoplasty. Postbronchodilator FEV&lt;sub&gt;1&lt;/sub&gt; averaged 83% to 84% at baseline and five years.&lt;br&gt;
&lt;br&gt;Respiratory adverse events declined sharply after one year and remained low until the end of follow-up, Gerard Cox, MBBS, reported at the American Thoracic Society meeting.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;Early on there were some concerns about the safety and durability of treatment with bronchial thermoplasty, and I think these data put those concerns to rest,&quot; Cox, of McMaster University in Hamilton, Ont., said in an interview.&lt;/p&gt;
&lt;p&gt;The long-term results come less than a month after the FDA approved the &lt;a href=&quot;http://www.medpagetoday.com/AllergyImmunology/Asthma/19805&quot; mce_href=&quot;http://www.medpagetoday.com/AllergyImmunology/Asthma/19805&quot; target=&quot;_blank&quot; title=&quot;FDA&amp;#8200;Approves&amp;#8200;First-of-a-Kind&amp;#8200;Asthma&amp;#8200;Device&quot;&gt;Alair system&lt;/a&gt; by Asthmatx of Sunnyvale, Calif.&lt;/p&gt;
&lt;p&gt;Bronchial thermoplasty works by administration of radiofrequency energy via a catheter inserted into a bronchoscope. The catheter tip expands until in contact with the airway walls, and the operator administers controlled thermal energy to ablate excess airway smooth muscle that contributes to asthma symptoms.&lt;/p&gt;
&lt;p&gt;Cox reported findings from a randomized clinical trial that initially included 55 patients treated with bronchial thermoplasty, 45 of whom agreed to participate in the long-term follow-up study. The trial included adults with FEV&lt;sub&gt;1&lt;/sub&gt; between 60% and 85% of predicted despite treatment with inhaled corticosteroids and a long-acting beta-agonist, and worsening on withdrawal of the beta-agonist.&lt;/p&gt;
&lt;p&gt;Cox reported that 42 of the 45 patients completed five years of follow-up.&lt;/p&gt;
&lt;p&gt;Mean prebronchodilator FEV&lt;sub&gt;1 &lt;/sub&gt;increased from 70% to 76% during the first year of follow-up, then remained stable at about 74% during years two through four, and averaged 70.6% at the end of follow-up.&lt;/p&gt;
&lt;p&gt;Baseline postbronchodilator FEV&lt;sub&gt;1&lt;/sub&gt; averaged 83.3%, ranged between 84% and 85% during years one through four, and stood at 83.7% after five years.&lt;/p&gt;
&lt;p&gt;Patients treated with bronchial thermoplasty had an average of 4.4 respiratory adverse events during the first year of follow-up.&lt;/p&gt;
&lt;p&gt;The adverse events, manifesting as worsening of asthma symptoms, were not unexpected, said Cox. They tended to arise within a day of treatment and resolved within seven days in most cases.&lt;/p&gt;
&lt;p&gt;During years two through five, the mean number of adverse events declined to 1.2 to 1.6 events per patient, per year.&lt;/p&gt;
&lt;p&gt;No pneumothorax, cardiac arrhythmias, or deaths resulted from the treatment, and no patient required intubation or mechanical ventilation.&lt;/p&gt;
&lt;p&gt;Cox said bronchial thermoplasty is approved for patients with persistent, moderate to severe asthma despite use of two controller medications. Patients with the most severe forms of asthma, such as those requiring systemic steroids, did not tolerate the procedure well and had severe asthma worsening afterward.&lt;/p&gt;
&lt;p&gt;The long-term clinical experience and FDA approval offer a lesson about the field of medicine&apos;s reaction to unconventional ideas, he added.&lt;/p&gt;
&lt;p&gt;&quot;This technology was soundly criticized when it was first introduced some years ago, as essentially heretical,&quot; said Cox. &quot;What has transpired over the past 10 years or so should make us realize that there are ideas that might sound strange when we first hear about them. What we should do is examine them rigorously, with rigorous science, not bias.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Cox reported no disclosures.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_1910"
                     title="ATS: Patients with PAH Maintain Long-Term Gains (CME/CE)"
                     score="-0.031"
                     href="http://www.medpagetoday.com/MeetingCoverage/ATS/tb/20257?impressionId=1283456788648"
                     
      NEW ORLEANS  --  Durable improvements were seen in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH) treated with an investigational promoter of nitric oxide signaling in a small trial.&lt;br&gt;
&lt;br&gt;A 60- to 70-meter improvement in the six-minute walk test at 12 weeks was maintained at 15 months in patients treated with riociguat. The proportion of patients in functional class I/II more than doubled during the first 12 weeks of treatment and continued to increase through the latest follow-up.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;&quot;The improvements seen in the original trial after 15 weeks, which were remarkable in themselves, were sustained during at least 15 months of long-term follow-up in both CTEPH and PAH patients,&quot; Hossein Ardeschir Ghofrani, MD, of Justus-Liebig University in Giessen, Germany, reported here at the American Thoracic Society meeting.&lt;/p&gt;
&lt;p&gt;&quot;Improvements in functional class were sustained and perhaps increased,&quot; according to Ghofrani. &quot;Riociguat at doses up to 2.5 mg [three times daily] was well tolerated and associated with a favorable safety profile.&quot;&lt;/p&gt;
&lt;p&gt;Riociguat stimulates soluble guanylate cyclase, a key enzyme in the nitric oxide signaling pathway, to trigger vasodilation. The drug sensitizes guanylate cyclase to nitric oxide and directly stimulates the enzyme independently of nitric oxide.&lt;/p&gt;
&lt;p&gt;In a 12-week open-label study, 78 patients with class II-III CTEPH or PAH received riociguat at doses titrated to a maximum of 7.5 mg/d, adjusted according to a prespecified systolic blood pressure range. Patients continued existing medication. The primary outcomes were six-minute walk test (distance), change in World Health Organization functional class, and safety.&lt;/p&gt;
&lt;p&gt;After 12 weeks, mean six-minute walk distance had increased from 365 m at baseline to 431 m. About 20% of patients were classified as WHO class I-II at the beginning of the study, increasing to 47% after 12 weeks. Improvement occurred in patients with CTEPH and PAH alike.&lt;/p&gt;
&lt;p&gt;Patients who completed the 12-week trial were eligible to enroll in a long-term extension, and 68 (41 with CTEPH and 27 with PAH) chose to do so. When the first patient reached 24 months of follow-up, the data from the extension phase were analyzed.&lt;/p&gt;
&lt;p&gt;Follow-up during the extension averaged 15 months. Ghofrani reported that 65 of the 68 patients remained alive, and 54 continued to take riociguat. Three-fourths of the patients tolerated the highest dose of the drug. Complete 15-month efficacy data were available for 31 patients.&lt;/p&gt;
&lt;p&gt;The six-minute walk distance averaged 430 m at 15 months. The proportion of patients in functional class I-II had increased to 53.2% in the CTEPH patients and 58.1% in the PAH group.&lt;/p&gt;
&lt;p&gt;The most common adverse events were peripheral edema and nasopharyngitis (12 patients each), hypotension (10), respiratory tract infection (eight) and syncope (seven, of which three were considered drug related). Ghofrani said none of the three deaths was related to the study drug.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by Bayer-Schering.&lt;/p&gt;&lt;p&gt;Ghofrani disclosed relationships with Pfizer, Actelion, Lilly, Bayer-Schering, United Therapeutics, GlaxoSmithKline, and Ergonex.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
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