Aspirin desensitization in patients with aspirin-induced and aspirin-tolerant asthma : a double-blind study

Background: Numerous open trials have demonstrated the beneficial clinical effects of aspirin desensitization (AD) in patients with aspirin-induced asthma (AIA). These beneficial effects might be attributable to aspirin’s potent antiinflammatory properties, but that supposition requires further corroboration. Objective: We sought to compare the clinical and biochemical responses to chronic oral AD in 20 patients with AIA and 14 patients with aspirin-tolerant asthma (ATA). All of the patients had chronic rhinosinusitis and nasal polyposis, and these responses were investigated in a pilot, double-blind, placebocontrolled study. Methods: Twelve patients with AIA and 6 patients with ATA were randomly assigned to receive 624 mg of aspirin, and 8 patients with AIA and 8 patients with ATA received placebo. Both aspirin and placebo were administered once daily for 6 months. Nasal symptoms, Sino-Nasal Outcome Test (SNOT20) scores, peak nasal inspiratory flows, Asthma Control Questionnaire scores, spirometric parameters, peak expiratory flows, blood eosinophilia, and corticosteroid doses were assessed on a monthly basis. Levels of urinary leukotriene E4 and the stable plasma prostaglandin (PG) D2 metabolite 9a,11b-PGF2 were evaluated at baseline and after 1, 3, 5, and 6 months. Results: Only the patients with AIA subjected to AD reported improvements in smell and reductions in sneezing and nasal blockade. The SNOT20 and Asthma Control Questionnaire scores of these patients decreased, and their peak nasal inspiratory flows increased. The dosages of inhaled corticosteroids were reduced. There were no changes in leukotriene E4 or 9a,11b-PGF2 levels after AD. Conclusion: The clinically beneficial effects of AD on nasal and bronchial symptoms occurred only in the patients with AIA

Subphenotypes of nonsteroidal antiinflammatory diseaseexacerbated respiratory disease identified by latent class analysis

Background Induced sputum (IS) allows to measure mediators of asthmatic inflammation in bronchial secretions. NSAID‐exacerbated respiratory disease (NERD) is recognized as a distinct asthma phenotype, usually with a severe course, eosinophilic airway inflammation, and increased production of pro‐inflammatory eicosanoids. A more insightful analysis of NERD patients has shown this phenotype to be nonhomogeneous. Objective We aimed to identify possible subphenotypes in a cohort of NERD patients with the means of latent class analysis (LCA). Methods A total of 95 asthma patients with aspirin hypersensitivity underwent sputum induction. High‐performance liquid chromatography or gas chromatography coupled with mass spectrometry was used to profile eicosanoids in induced sputum supernatant (ISS). Sixteen variables covering clinical characteristics, IS inflammatory cells, and eicosanoids were considered in the LCA. Results Three classes (subphenotypes) were distinguished within the NERD cohort. Class 1 subjects had mild‐to‐moderate asthma, an almost equal distribution of inflammatory cell patterns, the lowest concentrations of eicosanoids, and logLTE4/logPGE2 ratio. Class 2 represented severe asthma with impaired lung function despite high doses of steroids. High sputum eosinophilia was in line with higher pro‐inflammatory LTE4 in ISS and the highest logLTE4/logPGE2 ratio. Class 3 subjects had mild‐to‐moderate asthma and were also characterized by eosinophilic airway inflammation, yet increased production of pro‐ (LTE4, PGD2 and 11‐dehydro‐TBX2) was balanced by anti‐inflammatory PGE2. The value of logLTE4/logPGE2 was between values calculated for classes 1 and 3, similarly to disease control and severity. Conclusions LCA revealed three distinct NERD subphenotypes. Our results support a more complex pathobiology of aspirin hypersensitivity. Considering NERD heterogeneity, the relationship between inflammatory pathways and clinical manifestations of asthma may lead to more individualized treatment in difficult to treat patients in the future

Usefulness of combined endobronchial and endoscopic ultrasound-guided needle aspiration in the diagnosis of sarcoidosis : a prospective multicenter trial

Introduction Needle biopsy of enlarged lymph nodes is an accepted method for the diagnostic workup of sarcoidosis, but the optimal endosonography‑guided approach is yet to be determined. Objectives The aim of our study was to assess the relative diagnostic yield of combined ultrasound‑guided needle aspiration (CUS‑b‑NA), which includes endobronchial ultrasound‑guided transbronchial needle aspiration (EBUS‑TBNA) with endoscopic ultrasound fine‑needle aspiration (EUS‑b‑FNA), as well as the role of the cell block (CB) technique and lymph node localization in the diagnostic workup of sarcoidosis. Patients and methods This was a prospective multicenter study including consecutive patients with clinical suspicion of stage I or II sarcoidosis. CUS‑b‑NA with smears and CB technique were performed in the whole study group. If a biopsy result was not conclusive, an invasive diagnostic workup and a 6-month follow‑up were scheduled. Results Out of 77 screened patients, 54 signed written consent and 50 were enrolled for the final analysis. The overall sensitivity of EBUS‑TBNA, EUS‑b‑FNA, and CUS‑b‑NA was 76.6%, 70.2%, and 91.7%, respectively. There were no differences between EBUS‑TBNA and EUS‑b‑FNA (P = 0.52) but CUS‑b‑NA had a higher diagnostic yield (P = 0.005 and P = 0.001, respectively). Adding the CB method to smear technique (P = 0.008) and biopsy of the subcarinal lymph nodes increased the diagnostic yield (P = 0.001). Conclusions The diagnostic yield of CUS‑b‑NA is higher than that of endosonographic techniques alone in the diagnostic workup of stage I and II sarcoidosis. The preparation of cytological material including CB and the choice of the subcarinal lymph node station for the biopsy increase the diagnostic efficacy

A combined approach of endobronchial and endoscopic ultrasound-guided needle aspiration in the radiologically normal mediastinum in non-small-cell lung cancer staging--a prospective trial

This prospective study aimed to assess the diagnostic yield of the combined approach - endobronchial (EBUS) and endoscopic (EUS) ultrasound-guided needle aspiration (combined ultrasound-needle aspiration (CUS-NA)) in the radiologically normal mediastinum in non-small-cell lung cancer (NSCLC) staging. CUS-NA was performed simultaneously under local anaesthesia and sedation in consecutive NSCLC patients with mediastinal nodes that were not enlarged on CT (stage IA-IIB). All patients with negative CUS-NA subsequently underwent the transcervical extended bilateral mediastinal lymphadenectomy (TEMLA) as a confirmatory test. A total of 120 NSCLC patients underwent CUS-NA between 1 January 2008 and 31 December 2008. There were 318 mediastinal nodes biopsied (158 EBUS-NA - stations: 2R - 2, 2L - 1, 4R - 34, 4L - 33 and 7 - 88 and 160 EUS-NA - stations: 4L - 57, 7 - 101 and 9 - 2). CUS-NA revealed metastatic lymph node involvement in 19 of 120 patients (16%) and in 31 of 318 biopsies (10%). The prevalence was 22%. In 99 patients with negative CUS-NA, who underwent subsequent TEMLA, metastatic nodes were diagnosed in nine patients (8%) in 11 stations: 2R - 2, 4R - 4, 4L - 1, 5 - 3 and 7 - 1. In all but one patient there were 'minimal N2' only. Diagnostic sensitivity, specificity, total accuracy, positive predictive value (PPV) and negative predictive value (NPV) of CUS-NA for normal mediastinum was 68% (95% confidence interval (CI): 48-84), 98% (95% CI: 92-100), 91% (95% CI: 86-96), 91% (95% CI: 70-99) and 91% (95% CI: 83-96), respectively. The sensitivity of CUS-NA was significantly higher than with EBUS-NA alone (p=0.04) and higher, close to the level of significance than with EUS-NA alone (p=0.07). The NPV of all techniques was high and that of CUS-NA was significantly higher than EBUS-NA alone and EUS-NA alone (p=0.01, p=0.03). No complications of CUS-NA were observed. In the radiologically normal mediastinum, CUS-NA is a highly effective and safe technique in NSCLC staging and, if negative, a surgical diagnostic exploration of the mediastinum may be omitte