BACKGROUND Hereditary angioedema is characterized by recurrent attacks of angioedema of the skin, larynx, and gastrointestinal tract. Bradykinin is the key mediator of symptoms. Icatibant is a selective bradykinin B2 receptor antagonist. METHODS In two double-blind, randomized, multicenter trials, we evaluated the effect of icatibant in patients with hereditary angioedema presenting with cutaneous or abdominal attacks. In the For Angioedema Subcutaneous Treatment (FAST) 1 trial, patients received either icatibant or placebo; in FAST-2, patients received either icatibant or oral tranexamic acid, at a dose of 3 g daily for 2 days. Icatibant was given once, subcutaneously, at a dose of 30 mg. The primary end point was the median time to clinically significant relief of symptoms. RESULTS A total of 56 and 74 patients underwent randomization in the FAST-1 and FAST-2 trials, respectively. The primary end point was reached in 2.5 hours with icatibant versus 4.6 hours with placebo in the FAST-1 trial (P = 0.14) and in 2.0 hours with icatibant versus 12.0 hours with tranexamic acid in the FAST-2 trial (P<0.001). In the FAST-1 study, 3 recipients of icatibant and 13 recipients of placebo needed treatment with rescue medication. The median time to first improvement of symptoms, as assessed by patients and by investigators, was significantly shorter with icatibant in both trials. No icatibant-related serious adverse events were reported. CONCLUSIONS In patients with hereditary angioedema having acute attacks, we found a significant benefit of icatibant as compared with tranexamic acid in one trial and a nonsignificant benefit of icatibant as compared with placebo in the other trial with regard to the primary end point. The early use of rescue medication may have obscured the benefit of icatibant in the placebo trial. (Funded by Jerini; ClinicalTrials.gov numbers, NCT00097695 and NCT00500656.)

No abstract

To cite this article: Craig TJ, Bewtra AK, Bahna SL, Hurewitz D, Schneider LC, Levy RJ, Moy JN, Offenberger J, Jacobson KW, Yang WH, Eidelman F, Janss G, Packer FR, Rojavin MA, Machnig T, Keinecke H‐O, Wasserman RL. C1 esterase inhibitor concentrate in 1085 Hereditary Angioedema attacks – final results of the I.M.P.A.C.T.2 study. Allergy 2011; 66: 1604–1611. Abstract Background:  The placebo‐controlled study International Multicentre Prospective Angioedema C1‐INH Trial 1 (I.M.P.A.C.T.1) demonstrated that 20 U/kg C1 esterase inhibitor (C1‐INH) concentrate (Berinert®; CSL Behring, Marburg, Germany) is effective in treating acute abdominal and facial Hereditary Angioedema (HAE) attacks. Methods:  I.M.P.A.C.T.2 was an open‐label extension study of I.M.P.A.C.T.1 to evaluate the safety and efficacy of long‐term treatment with 20 U/kg C1‐INH for successive HAE attacks at any body location. Efficacy outcomes included patient‐reported time to onset of symptom relief (primary) and time to complete resolution of all symptoms (secondary), analysed on a per‐patient and per‐attack basis. Safety assessments included adverse events, vital signs, viral safety and anti‐C1‐INH antibodies. Results:  During a median study duration of 24 months, 1085 attacks were treated in 57 patients (10–53 years of age). In the per‐patient analysis, the median time to onset of symptom relief was 0.46 h and was similar for all types of attacks (0.39–0.48 h); the median time to complete resolution of symptoms was 15.5 h (shortest for laryngeal attacks: 5.8 h; 12.8–26.6 h for abdominal, peripheral and facial attacks). Demographic factors, type of HAE, intensity of attacks, time to treatment, use of androgens and presence of anti‐C1‐INH antibodies had no clinically relevant effect on the efficacy outcomes. There were no treatment‐related safety concerns. No inhibitory anti‐C1‐INH antibodies were detected in any patient. Conclusions:  A single dose of 20 U/kg C1‐INH concentrate is safe and provides reliable efficacy in the long‐term treatment of successive HAE attacks at any body location. See Special Feature Page for this article http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1398-9995/homepage/free_articles.htm

Pollen allergy has been found in 80–90% of childhood asthmatics and 40–50% of adult-onset asthmatics. Despite the high prevalence of atopy in asthmatics, a causal relationship between the allergic response and asthma has not been clearly established. Pollen grains are too large to penetrate the small airways where asthma occurs. Yet pollen cytoplasmic fragments are respirable and are likely correlated with the asthmatic response in allergic asthmatics. In this review, we outline the mechanism of pollen fragmentation and possible pathophysiology of pollen fragment-induced asthma. Pollen grains rupture within the male flowers and emit cytoplasmic debris when winds or other disturbances disperse the pollen. Peak levels of grass and birch pollen allergens in the atmosphere correlated with the occurrence of moist weather conditions during the flowering period. Thunderstorm asthma epidemics may be triggered by grass pollen rupture in the atmosphere and the entrainment of respirable-sized particles in the outflows of air masses at ground level. Pollen contains nicotinamide adenine dinucleotide phosphate (reduced) oxidases and bioactive lipid mediators which likely contribute to the inflammatory response. Several studies have examined synergistic effects and enhanced immune response from interaction in the atmosphere, or from co-deposition in the airways, of pollen allergens, endogenous pro-inflammatory agents, and the particulate and gaseous fraction of combustion products. Pollen and fungal fragments also contain compounds that can suppress reactive oxidants and quench free radicals. It is important to know more about how these substances interact to potentially enhance, or even ameliorate, allergic asthma.

BackgroundInadequate efficacy of current intranasal steroids in chronic rhinosinusitis (CRS) is attributable to ineffective and/or inconsistent drug delivery to target anatomic sites. A new exhalation delivery system with fluticasone (EDS‐FLU) may improve outcomes by significantly increasing superior/posterior corticosteroid delivery. A study was conducted to assess the long‐term efficacy and safety outcomes of EDS‐FLU in individuals with CRS.MethodsThis was a 12‐month, multicenter, single‐arm study evaluating the safety and efficacy of EDS‐FLU 372 μg twice daily in CRS patients (with [n = 34] or without [n = 189] nasal polyps [NP]). Efficacy assessments by serial nasal endoscopy and patient report included: 22‐item Sino‐Nasal Outcome Test (SNOT‐22), NP grade, standardized surgical indicator assessment, Lund‐Kennedy score, and Patient Global Impression of Change. Adverse event (AE) evaluations included nasal endoscopy. Additional safety and efficacy outcomes were assessed.ResultsOf 223 patients who received EDS‐FLU, 96% reported prior corticosteroid use and 29% prior sinus surgery. The EDS‐FLU AE profile was similar to conventional intranasal steroids studied in similar populations. Most patients (87%) reported symptom improvement. Through 12 months, mean SNOT‐22 scores improved by −21.5 and −21.1 for CRS with and without NP, respectively. Among patients with NP, 54.2% had polyp elimination in at least 1 nostril and 83.3% had ≥1‐point improvement in polyp grade.ConclusionOver 1 year of treatment in CRS with and without NP, EDS‐FLU 372 μg twice daily was well tolerated and produced improvements across a broad range of objective and subjective measures. EDS‐FLU may be a desirable new option for patients with this condition.