The future of allergic rhinitis management : a partnership between health care professionals and patients

Peer reviewe

Current controversies and challenges in allergic rhinitis management

There are many obstacles in the path of effective allergy management, in general, and allergic rhinitis (AR) control, in particular. Chief among them are: insufficient symptom relief in some patients provided by some currently considered first-line AR treatments in real life; an over-reliance on randomized controlled trials to direct AR guideline recommendations; the need for a broader interpretation of the AR evidence base (to include randomized controlled trials and real-life studies); poorly designed and interpreted studies; and lack of an AR control concept and common language of control. These controversies are fully reviewed here and challenging solutions have been presented.peerreview_statement: The publishing and review policy for this title is described in its Aims & Scope. aims_and_scope_url: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=ierm20status: publishe

Current controversies and challenges in allergic rhinitis management

There are many obstacles in the path of effective allergy management, in general, and allergic rhinitis (AR) control, in particular. Chief among them are: insufficient symptom relief in some patients provided by some currently considered first-line AR treatments in real life; an over-reliance on randomized controlled trials to direct AR guideline recommendations; the need for a broader interpretation of the AR evidence base (to include randomized controlled trials and real-life studies); poorly designed and interpreted studies; and lack of an AR control concept and common language of control. These controversies are fully reviewed here and challenging solutions have been presented

Tumor-conditional anti-CTLA4 uncouples antitumor efficacy from immunotherapy-related toxicity

While immune checkpoint blockade leads to potent antitumor efficacy, it also leads to immune-related adverse events in cancer patients. These toxicities stem from systemic immune activation resulting in inflammation of multiple organs, including the gastrointestinal tract, lung, and endocrine organs. We developed a dual variable domain immunoglobulin of anti-CTLA4 antibody (anti-CTLA4 DVD, where CTLA4 is defined as cytotoxic T lymphocyte-associated antigen-4) possessing an outer tumor-specific antigen-binding site engineered to shield the inner anti-CTLA4-binding domain. Upon reaching the tumor, the outer domain was cleaved by membrane type-serine protease 1 (MT-SP1) present in the tumor microenvironment, leading to enhanced localization of CTLA4 blockade. Anti-CTLA4 DVD markedly reduced multiorgan immune toxicity by preserving tissue-resident Tregs in Rag 1-/- mice that received naive donor CD4+ T cells from WT C57BL/6j mice. Moreover, anti-CTLA4 DVD induced potent antitumor effects by decreasing tumor-infiltrating Tregs and increasing the infiltration of antigen-specific CD8+ T lymphocytes in TRAMP-C2-bearing C57BL/6j mice. Treg depletion was mediated through the antibody-dependent cellular cytotoxicity (ADCC) mechanism, as anti-CTLA4 without the FcγR-binding portion (anti-CTLA4 DANA) spared Tregs, preventing treatment-induced toxicities. In summary, our results demonstrate an approach to anti-CTLA4 blockade that depletes tumor-infiltrating, but not tissue-resident, Tregs, preserving antitumor effects while minimizing toxicity. Thus, our tumor-conditional anti-CTLA4 DVD provides an avenue for uncoupling antitumor efficacy from immunotherapy-induced toxicities

Sectoral approaches to improve regional carbon budgets

Humans utilise about 40% of the earth’s net primary production (NPP) but the products of this NPP are often managed by different sectors, with timber and forest products managed by the forestry sector and food and fibre products from croplands and grasslands managed by the agricultural sector. Other significant anthropogenic impacts on the global carbon cycle include human utilization of fossil fuels and impacts on less intensively managed systems such as peatlands, wetlands and permafrost. A great deal of knowledge, expertise and data is available within each sector. We describe the contribution of sectoral carbon budgets to our understanding of the global carbon cycle. Whilst many sectors exhibit similarities for carbon budgeting, some key differences arise due to differences in goods and services provided, ecology, management practices used, landmanagement personnel responsible, policies affecting land management, data types and availability, and the drivers of change. We review the methods and data sources available for assessing sectoral carbon budgets, and describe some of key data limitations and uncertainties for each sector in different regions of the world. We identify the main gaps in our knowledge/data, show that coverage is better for the developed world for most sectors, and suggest how sectoral carbon budgets could be improved in the future. Research priorities include the development of shared protocols through site networks, a move to full carbon accounting within sectors, and the assessment of full greenhouse gas budgets