Chronic rhinosinusitis (CRS) is a complex disease consisting of several disease variants with different underlying pathophysiologies. Limited knowledge of the mechanisms of these disease subgroups is ...possibly the greatest obstacle in understanding the causes of CRS and improving treatment. It is generally agreed that there are clinically relevant CRS phenotypes defined by an observable characteristic or trait, such as the presence or absence of nasal polyps. Defining the phenotype of the patient is useful in making therapeutic decisions. However, clinical phenotypes do not provide full insight into all underlying cellular and molecular pathophysiologic mechanisms of CRS. Recognition of the heterogeneity of CRS has promoted the concept that CRS consists of multiple groups of biological subtypes, or “endotypes,” which are defined by distinct pathophysiologic mechanisms that might be identified by corresponding biomarkers. Different CRS endotypes can be characterized by differences in responsiveness to different treatments, including topical intranasal corticosteroids and biological agents, such as anti–IL-5 and anti-IgE mAb, and can be based on different biomarkers that are linked to underlying mechanisms. CRS has been regarded as a single disease entity in clinical and genetic studies in the past, which can explain the failure to identify consistent genetic and environmental correlations. In addition, better identification of endotypes might permit individualization of therapy that can be targeted against the pathophysiologic processes of a patient's endotype, with potential for more effective treatment and better patient outcomes.
Background Patients with chronic idiopathic urticaria/chronic spontaneous urticaria (CIU/CSU) often continue to experience symptoms despite receiving standard-of-care therapy with H1 -antihistamines ...along with 1 or more add-on therapies. Objectives We sought to evaluate the safety and efficacy of 24 weeks of treatment with omalizumab in patients with persistent CIU/CSU despite treatment with H1 -antihistamines at up to 4 times the approved dose plus H2 -antihistamines, leukotriene receptor antagonists, or both. Methods In this phase III study patients were randomized to receive 6 subcutaneous injections at 4-week intervals of either 300 mg of omalizumab or placebo, followed by a 16-week observation period. The primary objective of the study was to evaluate the overall safety of omalizumab compared with placebo. Efficacy (itch severity, hive, and urticaria activity scores) was evaluated at weeks 12 and 24. Results The overall incidence and severity of adverse events and serious adverse events were similar between omalizumab and placebo recipients; the safety profile was consistent with omalizumab in patients with allergic asthma. At week 12, the mean change from baseline in weekly itch severity score was −8.6 (95% CI, −9.3 to −7.8) in the omalizumab group compared with −4.0 (95% CI, −5.3 to −2.7) in the placebo group ( P < .001). Significant improvements were seen for additional efficacy end points at week 12; these benefits were sustained to week 24. Conclusion Omalizumab was well tolerated and reduced the signs and symptoms of CIU/CSU in patients who remained symptomatic despite the use of H1 -antihistamines (up to 4 times the approved dose) plus H2 -antihistamines, leukotriene receptor antagonists, or both.
Sublingual immunotherapy (SLIT) is increasingly used worldwide. Despite its safety being well ascertained, there is no universally accepted system to grade and classify its adverse events (AEs). ...According to the literature, it seems reasonable to classify and grade systemic side effects by using the previously published World Allergy Organization recommendations. On the other hand, local side effects are the most frequent with SLIT, sometimes leading to its discontinuation. Therefore grading of the severity of local side effects was perceived as necessary for the purpose of uniform reporting, classification, and quantification of this aspect. A World Allergy Organization Taskforce, after examining the available literature and the postmarketing surveillance data, proposed a clinically based grading of the severity of local AEs caused by SLIT. The use of the Medical Dictionary for Regulatory Activities nomenclature for AEs was also included in this context. The proposed grading system for SLIT-induced local reactions is expected to improve and harmonize surveillance and reporting of the safety of SLIT.
World Allergy Organization anaphylaxis guidelines: Summary Simons, F. Estelle R., MD, FRCPC; Ardusso, Ledit R.F., MD; Bilò, M. Beatrice, MD ...
Journal of allergy and clinical immunology,
03/2011, Letnik:
127, Številka:
3
Journal Article
Recenzirano
Odprti dostop
When indicated at any time during the episode, additional important steps include administering supplemental oxygen and maintaining the airway, establishing intravenous access and giving fluid ...resuscitation, and initiating cardiopulmonary resuscitation with continuous chest compressions before rescue breathing.\n Intravenous Chlorpheniramine or Diphenhydramine; Oral Cetirizine) Beta-2 Adrenergic Agonistsa (eg. Intravenous Hydrocortisone or Methylprednisolone; Oral Prednisone or Prednisolone) Strength of recommendation for use in anaphylaxisb C C C Pharmacologic effects At H1-receptor, inverse agonist effect; stabilize receptors in inactive conformation; decrease skin and mucosal symptoms At beta-2 receptor, increase bronchodilation Switch off transcription of activated genes that encode pro-inflammatory proteins; decrease late phase allergic response Clinical relevance Decrease itch, flush, urticaria, sneezing, and rhinorrhea, but are not life-saving because they do not prevent or relieve obstruction to airflow or hypotension/shock Decrease wheeze, cough and shortness of breath but are not life-saving because they do not prevent or relieve upper airway obstruction or hypotension/shock Onset of action takes several hours; therefore, are not life-saving in initial hours of an anaphylactic episode; used to prevent and relieve protracted or biphasic anaphylaxis; however, these effects have not been proven Potential adverse effects (usual dose) First-generation drugs cause drowsiness, somnolence, and impaired cognitive functionc Tremor, tachycardia, dizziness, jitteriness Unlikely during a short course Potential adverse effects (overdose) Extreme drowsiness, confusion, coma, respiratory depression, paradoxical central nervous system stimulation, eg. seizures in infants and children Headache, hypokalemia, vasodilation Unlikely Comment From 0 to 14 different H1-antihistamines,c and different dose regimens, are listed as adjunctive medications in anaphylaxis guidelines; role not proven Use in anaphylaxis is extrapolated from use in acute asthma; if given as adjunctive treatment for bronchospasm not relieved by epinephrine, should optimally be delivered by face mask and nebulization From 0 to 3 different glucocorticoids,d and different dose regimens,d are listed as adjunctive medications in anaphylaxis guidelines; role not proven Table 8 Second-Line Medications for Anaphylaxis Treatment Medication Epinephrine/adrenaline auto-injectora Epinephrine from an ampule/syringeb or prefilled syringec (alternative but not preferred formulations) Other aspects of discharge management Anaphylaxis emergency action plan (personalized, written) Medical identification (eg, bracelet, wallet card) Medical record electronic flag (or chart sticker) Emphasize the importance of follow-up, preferably with an allergy/immunology specialist Assessment of sensitization to allergen Before discharge, consider assessing sensitization to allergens suggested in the history of the acute episode, by measuring serum IgE levels to relevant allergen(s), if the test is availabled 3-4 weeks after the episode, confirm allergen sensitization using skin testse Challenge/provocation tests might be needed in some patients, for example, with food or medication allergy, in order to assess risk of future anaphylactic episodes furtherf Long-term risk reduction: avoidance and/or immunomodulation Food-triggered anaphylaxis: avoidance of relevant food(s) Stinging insect-triggered anaphylaxis: avoidance of stinging insects; subcutaneous venom immunotherapy (protects up to 80-90% of adults and 98% of children) Medication-triggered anaphylaxis: avoidance of relevant medications; if indicated, medically supervised desensitization in a healthcare setting according to published protocols Idiopathic anaphylaxis: for frequent episodes, consider glucocorticoid and H1-antihistamine prophylaxis for 2-3 months Optimal management of asthma and other concomitant diseases Table 9 Recommendations at Time of Discharge From the Healthcare Setting
Biologic and New Therapies in Asthma Tabatabaian, Farnaz; Ledford, Dennis K; Casale, Thomas B
Immunology and allergy clinics of North America,
05/2017, Letnik:
37, Številka:
2
Journal Article
Recenzirano
Several biologics are currently FDA approved for asthma that target Th2 high patients. Unfortunately, 50% of patients with severe asthma do not fit this phenotype of disease and have fewer effective ...therapeutic options. In the clinical setting, total IgE, FeNO and peripheral blood eosinophils are important tools in defining Th2 high patients with asthma. However, precise biomarkers to predict better response to one specific Th2 high asthma therapy versus another is lacking. It is important to recognize that none of the current medications targeting the Th2 pathway induces persistent immunomodulation or remission.
Should different normal values be used in different situations? ...what is the most accurate normal FEV1/FVC ratio? ...the ethnic mixture of patients in the current article does not permit an answer ...to the question of determination of the FEV1/FVC z score in Asian or other populations, in which normal data might not be as accurate and spirometric results might be more difficult to interpret.
Functional T-cell lymphocytopenia can result in a variety of organ-specific autoimmune diseases in animal models; autoreactive T cells undergo expansion as a mechanism of compensation for lymphopenia.
Stinging insect allergy: state of the art 2015 Tankersley, Michael S; Ledford, Dennis K
The journal of allergy and clinical immunology in practice (Cambridge, MA),
05/2015, Letnik:
3, Številka:
3
Journal Article
Recenzirano
Stinging insect allergy is responsible for more than 10% of all cases of anaphylaxis. The potential culprit insects are diverse and vary with geography. The incidence of insect allergy is declining ...in some areas and increasing in others, possibly due to effects of climate change, introduction of species into new areas, outdoor recreational activities, and movement of human populations that brings insects into contact with a greater number of people. Flying Hymenoptera and imported fire ant stings are responsible for the majority of patients evaluated for insect anaphylaxis. The most efficient means of identifying allergy to insects is skin testing although falsely positive and negative results occur. The limitations of testing coupled with the natural temporal variability of allergic sensitivity complicate the interpretation of test results. The clinical history is of paramount importance to be certain that the test results are relevant; therefore, screening or testing before a history of a sting reaction is not advisable. Mast cell disorders are associated with severe anaphylaxis from insect stings and should be considered in affected subjects. Insect immunotherapy, using venoms for most insects and whole-body extracts for imported fire ants, is proven effective in reducing the likelihood of anaphylaxis due to subsequent stings from 40%-60% to less than 5%. Future clinical application of component testing or in vitro cellular tests, such as the basophil activation test, may improve optimal choices for immunotherapy.
AEs of interest included diabetes mellitus, hypertension, lipid disorders, cataracts, depression and mania, skeletal conditions (osteoporosis and fractures), and pneumonia and opportunistic ...infections.
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