Background Aspirin-exacerbated respiratory disease (AERD), also known as Samter's triad or aspirin (ASA)-intolerant asthma, affects 7% of asthmatics and has a higher prevalence in those with chronic rhinosinusitis and concomitant nasal polyposis. ASA desensitization with daily ASA therapy is a uniquely beneficial treatment for this disease entity and has been shown to have a significant impact on symptom scores, polyp disease, and need for systemic corticosteroids. However, no long-term studies have demonstrated whether or not ASA therapy remains safe and beneficial for these patients beyond 5-10 years. Objective This study was designed to determine the clinical course of AERD patients desensitized between 1995 and 2010. Methods A 20-question survey was distributed to patients who successfully completed ASA desensitization between January 1995 and April 2010. The questions were designed to assess ASA safety and longitudinal effects of ASA therapy in AERD. Results Of the 285 patients contacted, 92 (32%) completed the questionnaire. Average length of follow-up was 15 years. Of survey responders, 35 patients had discontinued ASA therapy. Although adverse reactions occurred, many also discontinued due to lack of efficacy or need for surgery. For those remaining on ASA (62%), significant improvement in sense of smell, asthma, sinus, and allergic rhinitis scores were noted ( P ≤ .001). The majority of ASA patients (68%) had a positive response to treatment and did not require further sinus surgery. However, ASA therapy did not delay the time to next sinus/polyp surgery ( P = .27) or reduce total number of sinus surgeries ( P = .56) compared to those who stopped treatment. Nearly 85% of AERD patients on ASA therapy found it to be helpful in improving airway disease and quality of life. Conclusion Aspirin desensitization followed by daily maintenance ASA therapy appears to be safe and effective even after 10+ years of continuous use.
Osteoblastic migration and proliferation in response to growth factors are essential for skeletal development, bone remodeling, and fracture repair, as well as pathologic processes, such as metastasis. We studied migration in response to platelet-derived growth factor (PDGF, 10 ng/ml) in a wounding model. PDGF stimulated a twofold increase in migration of osteoblastic MC3T3-E1 cells and murine calvarial osteoblasts over 24-48 h. PDGF also stimulated a tenfold increase in 3H-thymidine (3H-TdR) incorporation in MC3T3-E1 cells. Migration and DNA replication, as measured by BrdU incorporation, could be stimulated in the same cell. Blocking DNA replication with aphidicolin did not reduce the distance migrated. To examine the role of mitogen-activated protein (MAP) kinases in migration and proliferation, we used specific inhibitors of p38 MAP kinase, extracellular signal regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). For these signaling studies, proliferation was measured by carboxyfluorescein diacetate succinimidyl ester (CFSE) using flow cytometry. Inhibition of the p38 MAP kinase pathway by SB203580 and SB202190 blocked PDGF-stimulated migration but had no effect on proliferation. Inhibition of the ERK pathway by PD98059 and U0126 inhibited proliferation but did not inhibit migration. Inhibition of JNK activity by SP600125 inhibited both migration and proliferation. Hence, the stimulation of migration and proliferation by PDGF occurred by both overlapping and independent pathways. The JNK pathway was involved in both migration and proliferation, whereas the p38 pathway was predominantly involved in migration and the ERK pathway predominantly involved in proliferation.
The majority of patients with AERD who experience respiratory symptoms with alcohol consumption describe improvement in this domain following aspirin desensitization.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.