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Medical Journal Review

November 2022

WAO Reviews – Editors' Choice

The WAO Reviews editors, Juan Carlos Ivancevich, MD, and John J. Oppenheimer, MD - FACAAI - FAAAAI, select articles on a monthly basis for their importance to clinicians who care for patients with asthma and allergic/immunologic diseases.

Allergen immunotherapy: Past, present and future
Durham SR, Shamji MH
Nature Reviews Immunology 2022 (17 October)

This is an excellent review on allergy immunotherapy by Drs Durham and Shamji. The authors begin from its origin reviewing subcutaneous immunotherapy and then explore sublingual immunotherapy for aeroallergy, noting its better safety profile, even discussing oral immunotherapy for peanut. They then explore recent research examining the mechanisms underlying immunotherapy-induced tolerance, which includes reduction of allergen-specific T helper 2 (TH2) cells, an induction of regulatory T and B cells, and production of IgG and IgA “blocking” antibodies. To better harness these mechanisms, novel strategies are being explored to achieve safer, effective, more convenient regimens and more durable long-term tolerance; these include: alternative routes for current immunotherapy approaches, novel adjuvants, use of recombinant allergens (including hypoallergenic variants) and combination of allergens with immune modifiers or monoclonal antibodies targeting the TH2 cell pathway.

Clinical indicators for asthma-COPD overlap: A systematic review and meta-analysis
Peng J, Wang M, Wu Y, Shen Y, Chen L
International Journal of Chronic Obstructive Pulmonary Disease 2022;17: 2567—2575

Some clinical indicators have been reported to be useful in differentiating asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) from pure asthma/COPD, but the results have been inconsistent. Thus, the aim of this study was to evaluate the diagnostic value of these indicators for ACO by performing a systematic review of the literature. The authors identified 48 eligible studies and the pooled results indicated that compared with pure asthma, ACO patients had lower levels of forced expiratory volume in the first second (FEV1)% predicted (pred) (SMD=−1.09, 95% CI −1.3 to −0.87), diffusion lung capacity for carbon monoxide (DLCO)% pred (SMD=−0.83, 95% CI −1.24 to −0.42), fractional exhaled nitric oxide (FeNO) (SMD=−0.23, 95% CI −0.36 to −0.11), and higher levels of induced sputum neutrophil (SMD = 0.51, 95% CI 0.21 to 0.81), circulating YKL-40 (SMD = 0.96, 95% CI 0.27 to 1.64). However, relative to COPD alone, ACO patients had higher levels of FEV1% pred (SMD = 0.15, 95% CI 0.05 to 0.26), DLCO% pred (SMD = 0.38, 95% CI 0.16 to 0.6), FeNO (SMD = 0.59, 95% CI 0.40 to 0.78), serum total immunoglobulin (Ig)E (SMD = 0.42, 95% CI 0.1 to 0.75), blood eosinophil (SMD = 0.44, 95% CI 0.29 to 0.59), induced sputum eosinophil (SMD = 0.62, 95% CI 0.42 to 0.83), and lower levels of induced sputum neutrophil (SMD=−0.48, 95% CI −0.7 to −0.27), circulating YKL-40 (SMD=−1.09, 95% CI −1.92 to −0.26). They concluded that via these indicators one could differentiate ACO from pure asthma/COPD.

Ever and cumulative occupational exposure and lung function decline in longitudinal population-based studies: A systematic review and meta-analysis
Rabbani G, Nimmi N, Benke GP et al
Occupational & Environmental Medicine 2022; Published online before print (24 October)

It is well known that adverse occupational exposures can accelerate age-related lung function decline. The aim of this study was to examine this association using findings reported by longitudinal population-based studies. The authors found that ever exposures to gases/fumes, vapors, gases, dusts, fumes (VGDF) and aromatic solvents were significantly associated with FEV1 decline in meta-analyses. Cumulative exposures for these three occupational agents observed a similar trend of FEV1 decline. Ever exposures to fungicides and cumulative exposures to biological dust, as well as fungicides and insecticides were associated with FEV1 decline in fixed-effect models only; while, no statistically significant association was observed between mineral dust, herbicides and metals and FEV1 decline in this meta-analyses. Overall, these pooled estimates from the longitudinal population-based studies have provided evidence that occupational exposures are associated with FEV1 decline. The authors conclude that specific exposure control and respiratory health surveillance are required to protect the lung health of the workers.

Dog ownership in infancy is protective for persistent wheeze in 17q21 asthma-risk carriers
Tutino M, Granell R, Curtin JA et al
Journal of Allergy & Clinical Immunology 2022; Published online ahead of print (20 October)

As noted by the authors asthma-associated SNPs from large GWAS studies only explain a fraction of genetic heritability. Potential causes of the missing heritability include broad phenotype definitions and gene-environment interactions (GxE). The mechanisms underlying GxE in asthma are poorly understood. Previous GxE studies on pet ownership showed discordant results.

The aim of this study was to examine the association of GxE between the 17q12-21 locus and pet ownership in infancy in relation to wheeze. Wheezing classes derived from five UK-based birth cohorts (latent class analysis) were used to study GxE between the 17q12-21 asthma-risk variant rs2305480 and dog and cat ownership in infancy, using multinomial logistic regression. 9149 children had both pet ownership and genotype data available. From this, the authors found that the rs2305480 G allele was associated with increased risk of Persistent Wheeze (additive model OR=1.37; CI=1.25-1.51). There was no evidence of an association between dog or cat ownership and wheeze. Furthermore, they found significant evidence of a GxE interaction between rs2305480 and dog ownership (P=8.3e-4) on Persistent Wheeze; amongst dog owners the G allele was no longer associated with an increased risk of Persistent Wheeze (additive model OR=0.95; CI=0.73-1.24). For those without pets, G allele was associated with increased risk of Persistent Wheeze (OR=1.61; CI=1.40-1.86). Among cat owners no such dampening of the genetic effect was observed.

Targeting B cells and plasma cells in autoimmune diseases: From established treatments to novel therapeutic approaches
Merino-Vico A, Frazzei G, van Hamburg JP, Tas SW
European Journal of Immunology 2022; Published online ahead of print (31 October) or

In this review article the authors provide an overview of novel strategies to target B lineage cells in autoimmune diseases, with the focus on rheumatic diseases. Both advanced therapies, that have recently become available, and more experimental treatments that may reach the clinic in the near future, are discussed.

Autoimmune diseases are characterized by the recognition of self-antigens by the immune system, which leads to inflammation and tissue damage. B cells are directly and indirectly involved in the pathophysiology of autoimmunity, both via antigen-presentation to T cells and production of proinflammatory cytokines and/or autoantibodies. Consequently, B lineage cells have been identified as therapeutic targets in autoimmune diseases. B cell depleting strategies have proven beneficial in the treatment of rheumatoid arthritis (RA), systemic lupus erythematous (SLE), ANCA-associated vasculitis (AAV), multiple sclerosis (MS), and a wide range of other immune-mediated inflammatory diseases (IMIDs). However, not all patients respond to treatment or may not reach (drug-free) remission. Moreover, B cell depleting therapies do not always target all B cell subsets, such as short-lived and long-lived plasma cells. The authors stress that these cells play an active role in autoimmunity and in certain diseases their depletion would be beneficial to achieve disease remission.


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