Drug-resistant tuberculosis

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IMPORTANCE: Allergic rhinitis affects up to 40% of the US population. To desensitize allergic individuals, subcutaneous injection immunotherapy or sublingual immunotherapy may be administered. In the United States, sublingual immunotherapy is not approved by the Food and Drug Administration. However, some US physicians use aqueous allergens, off-label, for sublingual desensitization.
OBJECTIVE: To systematically review the effectiveness and safety of aqueous sublingual immunotherapy for allergic rhinoconjunctivitis and asthma.
EVIDENCE ACQUISITION: The databases of MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials were searched through December 22, 2012. English-language randomized controlled trials were included if they compared sublingual immunotherapy with placebo, pharmacotherapy, or other sublingual immunotherapy regimens and reported clinical outcomes. Studies of sublingual immunotherapy that are unavailable in the United States and for which a related immunotherapy is unavailable in the United States were excluded. Paired reviewers selected articles and extracted the data. The strength of the evidence for each comparison and outcome was graded based on the risk of bias (scored on allocation, concealment of intervention, incomplete data, sponsor company involvement, and other bias), consistency, magnitude of effect, and the directness of the evidence.
RESULTS: Sixty-three studies with 5131 participants met the inclusion criteria. Participants' ages ranged from 4 to 74 years. Twenty studies (n = 1814 patients) enrolled only children. The risk of bias was medium in 43 studies (68%). Strong evidence supports that sublingual immunotherapy improves asthma symptoms, with 8 of 13 studies reporting greater than 40% improvement vs the comparator. Moderate evidence supports that sublingual immunotherapy use decreases rhinitis or rhinoconjunctivitis symptoms, with 9 of 36 studies demonstrating greater than 40% improvement vs the comparator. Medication use for asthma and allergies decreased by more than 40% in 16 of 41 studies of sublingual immunotherapy with moderate grade evidence. Moderate evidence supports that sublingual immunotherapy improves conjunctivitis symptoms (13 studies), combined symptom and medication scores (20 studies), and disease-specific quality of life (8 studies). Local reactions were frequent, but anaphylaxis was not reported.
CONCLUSIONS AND RELEVANCE: The overall evidence provides a moderate grade level of evidence to support the effectiveness of sublingual immunotherapy for the treatment of allergic rhinitis and asthma, but high-quality studies are still needed to answer questions regarding optimal dosing strategies. There were limitations in the standardization of adverse events reporting, but no life-threatening adverse events were noted in this review.
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BACKGROUND: It is estimated that up to 24% of the population in Germany suffers from allergic rhinoconjunctivitis and 5% from allergic asthma. Allergic rhinoconjunctivitis is closely related to other atopic diseases.
METHODS: This review is based on pertinent publications retrieved by a selective search of the Medline database, guidelines from Germany and abroad, and Cochrane meta-analyses.
RESULTS: Specific immunotherapy (SIT) is the only diseases-modifying treatment option for allergies. Meta-analysis reveals standardized mean differences in allergic rhinitis symptom scores of -0.73 for subcutaneous immunotherapy (SCIT) and -0.49 for sublingual immunotherapy (SLIT); the corresponding mean differences in medication scores are -0.57 and -0.32, respectively. The treatment should be carried out for at least three years. It is indicated when the symptoms are severe and allergen avoidance is not a realistic option. The efficacy of treatment depends on the allergen dose; thus, every allergen preparation should be evaluated individually, independent of route of administration. SCIT can cause systemic adverse effects, including anaphylaxis. SLIT is safer but often causes allergic symptoms of the oral mucosa at the beginning of treatment.
CONCLUSION: Even though the efficacy of SIT is well documented, it is still underused. SIT should be offered as standard treatment to patients suffering from allergic rhinitis.
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Mitogen-activated protein kinase phosphatase 1 (MKP-1) represses MAPK-driven signalling and plays an important anti-inflammatory role in asthma and airway remodelling. Although MKP-1 is corticosteroid-responsive and increased by cAMP-mediated signalling, the upregulation of this critical anti-inflammatory protein by long-acting β2-agonists and clinically-used corticosteroids has been incompletely examined to date.
To address this, we investigated MKP-1 gene expression and protein upregulation induced by two long-acting β2-agonists (salmeterol and formoterol), alone or in combination with the corticosteroid fluticasone propionate (abbreviated as fluticasone) in primary human airway smooth muscle (ASM) cells in vitro. β2-agonists increased MKP-1 protein in a rapid but transient manner, while fluticasone induced sustained upregulation. Together, long-acting β2-agonists increased fluticasone-induced MKP-1 and modulated ASM synthetic function (measured by interleukin 6 (IL-6) and interleukin 8 (IL-8) secretion). As IL-6 expression (like MKP-1) is cAMP/adenylate cyclase-mediated, the long-acting β2-agonist formoterol increased IL-6 mRNA expression and secretion. Nevertheless, when added in combination with fluticasone, β2-agonists significantly repressed IL-6 secretion induced by tumour necrosis factor α (TNFα). Conversely, as IL-8 is not cAMP-responsive, β2-agonists significantly inhibited TNFα-induced IL-8 in combination with fluticasone, where fluticasone alone was without repressive effect.
In summary, long-acting β2-agonists increase fluticasone-induced MKP-1 in ASM cells and repress synthetic function of this immunomodulatory airway cell type.