The introduction of personalized medicine (PM) has been a milestone in the history of medical therapy, because it has revolutionized the previous approach of treating the disease with that of treating the patient. It is known today that diseases can occur in different genetic variants, making specific treatments of proven efficacy necessary for a given endotype. Allergic diseases are particularly suitable for PM, because they meet the therapeutic success requirements, including a known molecular mechanism of the disease, a diagnostic tool for such disease, and a treatment blocking the mechanism. The stakes of PM in allergic patients are molecular diagnostics, to detect specific IgE to single-allergen molecules and to distinguish the causative molecules from those merely cross-reactive, pursuit of patient's treatable traits addressing genetic, phenotypic, and psychosocial features, and omics, such as proteomics, epi-genomics, metabolomics, and breathomics, to forecast patient's responsiveness to therapies, to detect biomarker and mediators, and to verify the disease control. This new approach has already improved the precision of allergy diagnosis and is likely to significantly increase, through the higher performance achieved with the personalized treatment, the effectiveness of allergen immunotherapy by enhancing its already known and unique characteristics of treatment that acts on the causes.
- Klíčová slova
- allergen immunotherapy, molecular diagnosis, omics, personalized medicine, treatable traits,
- MeSH
- alergeny MeSH
- alergie * diagnóza terapie MeSH
- desenzibilizace imunologická MeSH
- genomika MeSH
- individualizovaná medicína * MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- alergeny MeSH
Rationale: Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. Objectives: To develop an integrated understanding of the rare and common variants located in multiple loci that have been reported to contribute to the risk of disease. Methods: We performed deep targeted resequencing (3.69 Mb of DNA) in cases (n = 3,624) and control subjects (n = 4,442) across genes and regions previously associated with disease. We tested for associations between disease and 1) individual common variants via logistic regression and 2) groups of rare variants via sequence kernel association tests. Measurements and Main Results: Statistically significant common variant association signals occurred in all 10 of the regions chosen based on genome-wide association studies. The strongest risk variant is the MUC5B promoter variant rs35705950, with an odds ratio of 5.45 (95% confidence interval, 4.91-6.06) for one copy of the risk allele and 18.68 (95% confidence interval, 13.34-26.17) for two copies of the risk allele (P = 9.60 × 10-295). In addition to identifying for the first time that rare variation in FAM13A is associated with disease, we confirmed the role of rare variation in the TERT and RTEL1 gene regions in the risk of IPF, and found that the FAM13A and TERT regions have independent common and rare variant signals. Conclusions: A limited number of common and rare variants contribute to the risk of idiopathic pulmonary fibrosis in each of the resequencing regions, and these genetic variants focus on biological mechanisms of host defense and cell senescence.
- Klíčová slova
- disease risk alleles, genetic variants, idiopathic pulmonary fibrosis, rare variants, targeted resequencing,
- MeSH
- ABC transportéry genetika MeSH
- celogenomová asociační studie MeSH
- DNA-helikasy genetika MeSH
- exoribonukleasy genetika MeSH
- genetická predispozice k nemoci MeSH
- genetická variace MeSH
- idiopatická plicní fibróza genetika MeSH
- interakce hostitele a patogenu genetika MeSH
- lidé MeSH
- logistické modely MeSH
- mucin 5B genetika MeSH
- promotorové oblasti (genetika) genetika MeSH
- protein A asociovaný s plicním surfaktantem genetika MeSH
- protein C asociovaný s plicním surfaktantem genetika MeSH
- proteiny aktivující GTPasu genetika MeSH
- proteiny vázající telomery genetika MeSH
- RNA genetika MeSH
- sekvenční analýza DNA MeSH
- stárnutí buněk genetika MeSH
- studie případů a kontrol MeSH
- telomerasa genetika MeSH
- vysoce účinné nukleotidové sekvenování MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- ABC transportéry MeSH
- ABCA3 protein, human MeSH Prohlížeč
- DNA-helikasy MeSH
- exoribonukleasy MeSH
- FAM13A protein, human MeSH Prohlížeč
- MUC5B protein, human MeSH Prohlížeč
- mucin 5B MeSH
- poly(A)-specific ribonuclease MeSH Prohlížeč
- protein A asociovaný s plicním surfaktantem MeSH
- protein C asociovaný s plicním surfaktantem MeSH
- proteiny aktivující GTPasu MeSH
- proteiny vázající telomery MeSH
- RNA MeSH
- RTEL1 protein, human MeSH Prohlížeč
- SFTPA2 protein, human MeSH Prohlížeč
- SFTPC protein, human MeSH Prohlížeč
- telomerasa MeSH
- telomerase RNA MeSH Prohlížeč
- TERT protein, human MeSH Prohlížeč
- TINF2 protein, human MeSH Prohlížeč
BACKGROUND: Allergic rhinitis (AR) affects 10% to 40% of the population. It reduces quality of life and school and work performance and is a frequent reason for office visits in general practice. Medical costs are large, but avoidable costs associated with lost work productivity are even larger than those incurred by asthma. New evidence has accumulated since the last revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines in 2010, prompting its update. OBJECTIVE: We sought to provide a targeted update of the ARIA guidelines. METHODS: The ARIA guideline panel identified new clinical questions and selected questions requiring an update. We performed systematic reviews of health effects and the evidence about patients' values and preferences and resource requirements (up to June 2016). We followed the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence-to-decision frameworks to develop recommendations. RESULTS: The 2016 revision of the ARIA guidelines provides both updated and new recommendations about the pharmacologic treatment of AR. Specifically, it addresses the relative merits of using oral H1-antihistamines, intranasal H1-antihistamines, intranasal corticosteroids, and leukotriene receptor antagonists either alone or in combination. The ARIA guideline panel provides specific recommendations for the choice of treatment and the rationale for the choice and discusses specific considerations that clinicians and patients might want to review to choose the management most appropriate for an individual patient. CONCLUSIONS: Appropriate treatment of AR might improve patients' quality of life and school and work productivity. ARIA recommendations support patients, their caregivers, and health care providers in choosing the optimal treatment.
- Klíčová slova
- Allergic rhinitis, practice guideline,
- MeSH
- alergická rýma farmakoterapie epidemiologie MeSH
- antagonisté histaminu H1 terapeutické užití MeSH
- antialergika terapeutické užití MeSH
- bronchiální astma prevence a kontrola MeSH
- dítě MeSH
- klinické rozhodování MeSH
- kvalita života MeSH
- lékařská praxe založená na důkazech MeSH
- lidé MeSH
- zvířata MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- směrnice pro lékařskou praxi MeSH
- Názvy látek
- antagonisté histaminu H1 MeSH
- antialergika MeSH
