Antileukotriene drugs in the treatment of obstructive lung diseases and rhinitis

Ostatnio opublikowane międzynarodowe raporty: Światowej Inicjatywy Zwalczania Astmy, PRACTicing ALLergology i Allergic Rhinitis and its Impact on Asthma rekomendują leki przeciwleukotrienowe w terapii astmy u dorosłych i u dzieci oraz w alergicznym nieżycie nosa. W niniejszym artykule przedstawiono argumenty za i przeciw lekom antyleukotrienowym w leczeniu obturacji dróg oddechowych.Recently published international recommendations including Global INitiative for Asthma, PRACTicing ALLergology and Allergic Rhinitis and its Impact on Asthma offer antileukotriene drugs for adult and childhood asthma and allergic rhinitis. In this article we discuss the arguments for and against antileukotriene drugs therapy in the treatment of obstructive lung diseases and rhinitis

Neurofibromatosis type 1 in an adult diagnosed by a pulmonologist

Nerwiakowłókniakowatość typu 1 jest częstą chorobą genetyczną wynikającą z braku białka neurofibrominy i w konsekwencji prowadzącą do różnych nieprawidłowości w obrębie obwodowego i ośrodkowego układu nerwowego, a także w innych narządach. Najczęściej rozpoznawana jest przez pediatrów w wieku dziecięcym. Zdarza się, że pozostaje nierozpoznana lub rozpoznana dopiero w wieku dorosłym. W niniejszej pracy przedstawiamy 32-letnią chorą, u której nerwiakowłókniakowatość typu 1 rozpoznano po skierowaniu jej do pulmonologa z podejrzeniem guza płuca lewego. Chorą przyjęto do Kliniki Pulmonologii do diagnostyki zacienienia w lewym płucu, stwierdzonego w badaniu rentgenowskim klatki piersiowej. W badaniu przedmiotowym stwierdzono na skórze ciała kilka plamistych przebarwień oraz guzków, które histologicznie okazały się nerwiakowłókniakami. Dalsza diagnostyka, obejmująca TK i PET klatki piersiowej oraz badanie okulistyczne, pozwoliła na rozpoznanie nerwiakowłókniakowatości typu 1.Neurofibromatosis type 1 (NF1), referred to as von Recklinghausen’s disease, is a genetic disorder triggered by mutation of the NF1 gene, resulting in a lack of neurofibromin, which leads to abnormalities found in the peripheral nervous system and central nervous system, as well as in other organs. The disease is diagnosed early, usually in childhood by pediatricians. However, in some cases, the disease is clinically silent and remains undiagnosed or is recognized in the late adulthood. We report a case study of a 32-year-old female, who was referred to the pulmunologist with a suspicion of a lung tumor. The patient was admitted to the Pulmonology Department to investigate further the subpleural mass localized in the left lung found by chance in a chest X-ray. Physical examination revealed café-au-lait spots on her skin, several subcutaneous nodules which were confirmed by a histopathology to be consistent with neurofibroma. Further diagnostic testing, such as chest CT, PET and ophthalmological examination, led to diagnosis of neurofibromatosis type 1 with pulmonary involvement

Unfavorably altered fibrin clot properties in patients with eosinophilic granulomatosis with polyangiitis (Churg-Strauss Syndrome) : association with thrombin generation and eosinophilia

Given reports on the increased prevalence of thromboembolic incidents in patients with eosinophilic granulomatosis with polyangiitis (EGPA; Churg-Strauss syndrome), we investigated whether fibrin clot properties are unfavorably altered in EGPA.Ex vivo plasma fibrin clot characteristics, including clot permeability, turbidimetry and efficiency of fibrinolysis using two assays, were investigated in 34 consecutive patients with remission in EGPA according to the Birmingham Vasculitis Activity Score version 3 (23 female, 11 male), aged 48 (range, 21-80) years. The control group comprised 34 age- and sex- matched volunteers.Compared with controls, patients with EGPA were characterized by denser fiber clots (estimated pore size, Ks, 7.30±0.93 vs 10.14±1.07 10-9 cm2), faster fibrin polymerization (lag phase in a turbidimetric curve, 41.8±3.6 vs 47.4±2.9 s), thicker fibrin fibers (maximum absorbance, ΔAbs, 0.87±0.09 vs 0.72±0.07), higher maximum levels of D-dimer released from clots (DDmax 4.10±0.46 vs 3.54±0.35 mg/L), and prolonged clot lysis time (t50%; 9.50±1.45 vs 7.56±0.87 min); all p<0.0001. Scanning electron microscopy images confirmed denser plasma fibrin networks composed of thinner fibers formed in EGPA. Antineutrophil cytoplasmic antibody status and C-reactive protein did not affect clot variables. Multivariate analysis adjusted for fibrinogen showed that Ks was predicted by eosinophil count, peak thrombin generation, factor VIII, and soluble CD40 ligand, whereas eosinophil count, peak thrombin generation and antiplasmin predicted t50%.This study is the first to show that EGPA is associated with prothrombotic plasma fibrin clot phenotype, which may contribute to thromboembolic manifestations reported in this disease

Increased activity of lipoprotein-associated phospholipase A2 in non-severe asthma

Background Given increased risk of cardiovascular events in asthma we hypothesized that lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme involved in atherosclerosis, is associated with proinflammatory and prothrombotic blood alterations in this disease. Methods In 164 adult asthmatics (63 with severe asthma) we measured plasma Lp-PLA2 activity using the PLAC test. We determined its relations to inflammation and prothrombotic blood alterations. Results In asthma, Lp-PLA2 was inversely related to the age (β = −0.1 [−0.18 to −0.02]) and was lower in women (n = 122 [74%], 205 [182–242] vs. 243 [203–262] nmol/min/ml, p = 0.001). Interestingly, Lp-PLA2 correlated negatively with the asthma severity score (β = −0.15 [−0.23 to −0.07]), being 10.3% higher in those with non-severe (mild or moderate) asthma (n = 101, 62%) as compared to the severe disease subtype (224 [191–261] vs. 203 [181–229], p = 0.006 after adjustment for potential confounders). Lp-PLA2 activity was positively related to the levels of low-density lipoprotein (β = 0.1 [0.02–0.18]), triglycerides (β = 0.11 [0.03–0.19]) and glucose (β = 0.1 [0.02–0.18]) and inversely to the tumor necrosis factor α (β = −0.27 [−0.35 to −0.2]), high sensitivity C-reactive protein (β = −0.1 [−0.19 to −0.02]) and fibrinogen (β = −0.12 [−0.21 to −0.03]), as well as prothrombin (β = −0.16 [−0.24 to −0.08]), and parameters describing thrombin generation potential, such as endogenous thrombin potential (β = −0.14 [−0.21 to −0.06]) and peak thrombin generated (β = −0.2 [−0.28 to −0.12]). Conclusions Elevated Lp-PLA2 activity in non-severe asthmatics suggests increased atherosclerotic risk in this group. Lower Lp-PLA2 activity accompanied by its inverse relationship to inflammatory or prothrombotic blood biomarkers observed in turn in severe asthmatics might be related to the pathogenesis of more severe asthma phenotype

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

Severe dilated cardiomyopathy as a complication of well controlled Churg-Strauss syndrome

We present a case of a 42 year-old male with Churg-Strauss syndrome (CSS), who despite clinical remission developed severe dilated cardiomyopathy. Intensified immunosuppression helped to improve heart function. As heart involvement in CSS is very common, and may occur without prior symptoms, magnetic resonance imaging is advisable to identify patients with heart damage and introduce proper treatmen