EAACI Guidelines on Allergen Immunotherapy: House dust mite‐driven allergic asthma

Allergen immunotherapy (AIT) has been in use for the treatment of allergic disease for more than 100 years. Asthma treatment relies mainly on corticosteroids and other controllers recommended to achieve and maintain asthma control, prevent exacerbations, and improve quality of life. AIT is underused in asthma, both in children and in adults. Notably, patients with allergic asthma not adequately controlled on pharmacotherapy (including biologics) represent an unmet health need. The European Academy of Allergy and Clinical Immunology has developed a clinical practice guideline providing evidence‐based recommendations for the use of house dust mites (HDM) AIT as add‐on treatment for HDM‐driven allergic asthma. This guideline was developed by a multi‐disciplinary working group using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. HDM AIT was separately evaluated by route of administration and children and adults: subcutaneous (SCIT) and sublingual AIT (SLIT), drops, and tablets. Recommendations were formulated for each. The important prerequisites for successful treatment with HDM AIT are (a) selection of patients most likely to respond to AIT and (b) use of allergen extracts and desensitization protocols of proven efficacy. To date, only AIT with HDM SLIT‐tablet has demonstrated a robust effect in adults for critical end points (exacerbations, asthma control, and safety). Thus, it is recommended as an add‐on to regular asthma therapy for adults with controlled or partially controlled HDM‐driven allergic asthma (conditional recommendation, moderate‐quality evidence). HDM SCIT is recommended for adults and children, and SLIT drops are recommended for children with controlled HDM‐driven allergic asthma as the add‐on to regular asthma therapy to decrease symptoms and medication needs (conditional recommendation, low‐quality evidence).     

Prevalence and management of chronic insomnia in Swiss primary care: Cross‐sectional data from the “Sentinella” practice‐based research network

We investigated the prevalence and treatment of patients with chronic insomnia presenting to Swiss primary care physicians (PCPs) part of “Sentinella”, a nationwide practice‐based research network. Each PCP consecutively asked 40 patients if they had sleep complaints, documented frequency, duration, comorbidities, and reported ongoing treatment. We analysed data of 63% (83/132) of the PCPs invited. The PCPs asked 76% (2,432/3,216) of included patients about their sleep (51% female); 31% (761/2,432) of these had had insomnia symptoms; 36% (875/2,432) had current insomnia symptoms; 11% (269/2,432) met the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM‐5) criteria for chronic insomnia (61% female). In all, 75% (201/269) of patients with chronic insomnia had comorbidities, with 49% (99/201) reporting depression. Chronic insomnia was treated in 78% (209/269); 70% (188/268) took medication, 38% (102/268) benzodiazepines or benzodiazepine receptor agonists, 32% (86/268) took antidepressants. Only 1% (three of 268) had been treated with cognitive behavioural therapy for insomnia (CBT‐I). A third of patients presenting for a non‐urgent visit in Swiss primary care reported insomnia symptoms and 11% met the DSM‐5 criteria for chronic insomnia. Hypnotics were the most common treatment, but almost no patients received first‐line CBT‐I. Reducing the burden of insomnia depends on disseminating knowledge about and access to CBT‐I, and encouraging PCPs to discuss it with and offer it as a first‐line treatment to patients with chronic insomnia.     

EAACI position statement on asthma exacerbations and severe asthma

Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult‐to‐treat asthma and severe treatment‐resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment‐resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult‐to‐control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult‐to‐control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.     

EUFOREA consensus on biologics for CRSwNP with or without asthma

Novel therapies such as type 2 targeting biologics are emerging treatment options for patients with chronic inflammatory respiratory diseases, fulfilling the needs of severely uncontrolled patients. The majority of patients with chronic rhinosinusitis with nasal polyps (CRSwNP) and over half of patients with asthma show a type 2 inflammatory signature in sinonasal mucosa and/or lungs. Importantly, both chronic respiratory diseases are frequent comorbidities, ensuring alleviation of both upper and lower airway pathology by systemic biological therapy. Type 2‐targeting biologics such as anti‐IgE, anti‐IL4Rα, anti‐IL5, and anti‐IL5Rα have entered the market for selected pheno/endotypes of asthma patients and may soon also become available for CRSwNP patients. Given the high prevalence of chronic respiratory diseases and the high cost associated with biologics, patient selection is crucial in order to implement such therapies into chronic respiratory disease care pathways. The European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) organized a multidisciplinary Expert Board Meeting to discuss the positioning of biologics into the care pathways for CRSwNP patients with and without comorbid asthma.     

The burden of nonadherence among adults with asthma: a role for shared decision‐making

A shared approach to decision‐making framework has been suggested for chronic disease management especially where multiple treatment options exist. Shared decision‐making (SDM) requires that both physician and patients are actively engaged in the decision‐making process, including information exchange; expressing treatment preferences; as well as agreement over the final treatment decision. Although SDM appears well supported by patients, practitioners and policymakers alike, the current challenge is to determine how best to make SDM a reality in everyday clinical practice. Within the context of asthma, adherence rates are poor and are linked to outcomes such as reduced asthma control, increased symptoms, healthcare expenditures, and lower patient quality of life. It has been suggested that SDM can improve treatment adherence and that ignoring patients’ personal goals and preferences may result in reduced rates of adherence. Furthermore, understanding predictors of poor treatment adherence is a necessary step toward developing effective strategies to improve the patient‐reported and clinically important outcomes. Here, we describe why a shared approach to treatment decision‐making for asthma has the potential to be an effective tool for improving adherence, with associated clinical and patient‐related outcomes. In addition, we explore insights into the reasons why SDM has not been implemented into routine clinical practice.     

Patient‐shared TCRβ‐CDR3 clonotypes correlate with favorable prognosis in chronic hepatitis B

The presence of shared T‐cell clonotypes was found in several different diseases, but its relationship with the progression of disease remains unclear. By sequencing the complementary determining region 3 of T‐cell receptor (TCR) β chains from the purified antigen‐experienced CD8⁺ T cells, we characterized the T‐cell repertoire in a prospective cohort study among 75 patients with chronic hepatitis B in China, as well as a healthy control and a validation cohort. We found that most T‐cell clones from patients harbored the “patient‐specific” TCR sequences. However, “patient‐shared” TCR clonotypes were also widely found, which correlated with the favorable turnover of disease. Interestingly, the frequency of the “patient‐shared” clonotypes can serve as a biomarker for favorable prognosis. Based on the clonotypes in those patients with favorable outcomes, we created a database including several clusters of protective anti‐HBV CD8⁺ T‐cell clonotypes that might be a reasonable target for therapeutic vaccine development or adoptive cell transfer therapy. These findings were validated in an additional independent cohort of patients. These results suggest that the “patient‐shared” TCR clonotypes may serve as a valuable prognostic tool in the treatment of chronic hepatitis B and possibly other chronic viral diseases.     

Real-world Evaluation of Asthma Control and Treatment (REACT): findings from a national Web-based survey

BACKGROUND: Despite health initiatives for advancing the management of asthma, evidence suggests that many asthmatic subjects have uncontrolled disease. However, the prevalence of uncontrolled asthma in the United States is not known and has not been fully characterized. OBJECTIVE: We sought to assess the prevalence, morbidity, and factors associated with uncontrolled asthma in a nationally representative sample of patients with moderate-to-severe asthma using standard asthma medications. METHODS: A Web-based survey was administered to patients with diagnoses of asthma for at least 1 year who were receiving multiple controller medications. The Asthma Control Test score was used to stratify respondents into controlled and uncontrolled cohorts. RESULTS: A total of 1812 patients were assessed; 809 (45%) had controlled asthma, and 1003 (55%) had uncontrolled asthma. Most patients had health care coverage and received care from a general practitioner; a large proportion of patients with controlled asthma (74%) and patients with uncontrolled asthma (65%) reported never receiving an asthma action plan. Inhaled corticosteroid plus long-acting beta-agonist was the most common medication regimen in patients with controlled asthma (60%) and patients with uncontrolled asthma (48%) patients. Patients with uncontrolled asthma reported significantly higher rates of health care use. Several comorbidities were predictive of uncontrolled asthma. CONCLUSION: Uncontrolled asthma is highly prevalent (55%) in patients using standard asthma medications. There is need for improved asthma care in patients with moderate-to-severe asthma, including a global evaluation of asthma control, implementation of treatment plans and asthma control tests, and addressing comorbid conditions. CLINICAL IMPLICATIONS: Improved asthma care requires broader assessments of asthma control, including asthma-related health care and medication use, comorbidities, and the implementation of treatment plans and formal asthma control tests.     

Do mast cells link obesity and asthma?

Asthma is a chronic inflammatory disease of the lungs. Both the number of cases and severity of asthma have been increasing without a clear explanation. Recent evidence suggests that obesity, which has also been increasing alarmingly, may worsen or precipitate asthma, but there is little evidence of how obesity may contribute to lung inflammation. We propose that mast cells are involved in both asthma and obesity by being the target and source of adipocytokines, ‘alarmins’ such as interleukin‐9 (IL‐9) and interleukin‐33 (IL‐33), and stress molecules including corticotropin‐releasing hormone (CRH) and neurotensin (NT), secreted in response to the metabolic burden. In particular, CRH and NT have synergistic effects on mast cell secretion of vascular endothelial growth factor (VEGF). IL‐33 augments VEGF release induced by substance P (SP) and tumor necrosis factor (TNF) release induced by NT. Both IL‐9 and IL‐33 also promote lung mast cell infiltration and augment allergic inflammation. These molecules are also expressed in human mast cells leading to autocrine effects. Obese patients are also less sensitive to glucocorticoids and bronchodilators. Development of effective mast cell inhibitors may be a novel approach for the management of both asthma and obesity. Certain flavonoid combinations may be a promising new treatment approach.     

A comparative study of the frequency of antibody and titers against human herpesvirus 8 latent and lytic antigens in “at‐risk” individuals and among patients with Kaposi's sarcoma

Differences in the prevalence of human herpesvirus 8 (HHV‐8) and Kaposi's sarcoma (KS) have been described, depending on the study population and their geographic origin. A cross‐ sectional study aimed at detecting the frequency and titers of antibodies against HHV‐8 latent and lytic antigens in serum samples from individuals with different risk‐factors for HHV‐8 infection, as well as predictive marker identification in patients with KS, was conducted. Serum samples were collected from seven groups of individuals: 75 patients with AIDS‐KS, 5 with classic KS, 16 with African KS, 495 with HIV/AIDS, 805 patients with chronic kidney disease, 683 handicapped individuals, and 757 health care workers. Samples were evaluated for the presence and titers of HHV‐8‐specific antibodies to latent and lytic antigens using “in house” immunofluorescence assays. The results were analyzed by the Chi‐square, Fisher's exact test, Kruskal–Wallis and/or Mann–Whitney U‐tests. The frequencies of HHV‐8 antibodies were as follows: 87.5–100% in patients with KS, 20.4% in patients with HIV/AIDS, 18% in patients with chronic kidney disease, 1.6% in handicapped individuals, and 1.1% in health care workers. A greater number of samples were antibody positive to lytic antigens. Elevated titers of antibodies to latent and lytic antigens, mostly among patients with KS, were detected. Using established serological assays, different “at‐risk” populations for HHV‐8 infection/disease were detected in this geographic area, confirming HIV/AIDS and identifying patients with chronic kidney disease as high‐risk groups. It is suggested that a longitudinal evaluation of antibody titers in patients with chronic kidney disease be undertaken to confirm their predictive value in the development of KS. J. Med. Virol. 81:1292–1297, 2009. © 2009 Wiley‐Liss, Inc.     

Diagnosis and management of NSAID‐Exacerbated Respiratory Disease (N‐ERD)—a EAACI position paper

NSAID‐exacerbated respiratory disease (N‐ERD) is a chronic eosinophilic, inflammatory disorder of the respiratory tract occurring in patients with asthma and/or chronic rhinosinusitis with nasal polyps (CRSwNP), symptoms of which are exacerbated by NSAIDs, including aspirin. Despite some progress in understanding of the pathophysiology of the syndrome, which affects 1/10 of patients with asthma and rhinosinusitis, it remains a diagnostic and therapeutic challenge. In order to provide evidence‐based recommendations for the diagnosis and management of N‐ERD, a panel of international experts was called by the EAACI Asthma Section. The document summarizes current knowledge on the pathophysiology and clinical presentation of N‐ERD pointing at significant heterogeneity of this syndrome. Critically evaluating the usefulness of diagnostic tools available, the paper offers practical algorithm for the diagnosis of N‐ERD. Recommendations for the most effective management of a patient with N‐ERD stressing the potential high morbidity and severity of the underlying asthma and rhinosinusitis are discussed and proposed. Newly described sub‐phenotypes and emerging sub‐endotypes of N‐ERD are potentially relevant for new and more specific (eg, biological) treatment modalities. Finally, the document defines major gaps in our knowledge on N‐ERD and unmet needs, which should be addressed in the future.     

The use of omalizumab in allergen immunotherapy

Although omalizumab (anti‐IgE) is currently only approved for the treatment of asthma and chronic idiopathic urticaria, it has also been studied as an off‐label treatment for numerous allergic conditions, including use as an adjunct to allergen immunotherapy in the treatment of allergic rhinitis, asthma, venom hypersensitivity and food allergy. We conducted a review of publications involving the use of omalizumab with allergen immunotherapy, by searching PubMed with key search terms of “omalizumab” and “immunotherapy.” Omalizumab has been used in combination with inhalant allergen immunotherapy for the treatment of seasonal allergic rhinitis and comorbid asthma. While there have been no randomized controlled trials evaluating the addition of omalizumab to venom IT, several case reports and small patient series have been published on the use of omalizumab with venom IT. Omalizumab has been used in conjunction with oral immunotherapy for the treatment of milk, peanut and egg, as well as other foods in multi‐allergen protocols. In conclusion, omalizumab used in conjunction with immunotherapy has shown promising results, especially in the reduction of adverse reactions. At this stage, larger, randomized, placebo‐controlled trials are needed to better identify those patients who would benefit the most from the addition of omalizumab to immunotherapy, as well as optimal dosing strategies and duration of treatment.     

The axis of the receptor for advanced glycation endproducts in asthma and allergic airway disease

Asthma is a generalized term that describes a scope of distinct pathologic phenotypes of variable severity, which share a common complication of reversible airflow obstruction. Asthma is estimated to affect almost 400 million people worldwide, and nearly ten percent of asthmatics have what is considered “severe” disease. The majority of moderate to severe asthmatics present with a “type 2-high” (T2-hi) phenotypic signature, which pathologically is driven by the type 2 cytokines Interleukin-(IL)-4, IL-5, and IL-13. However, “type 2-low” (T2-lo) phenotypic signatures are often associated with more severe, steroid-refractory neutrophilic asthma. A wide range of clinical and experimental studies have found that the receptor for advanced glycation endproducts (RAGE) plays a significant role in the pathogenesis of asthma and allergic airway disease (AAD). Current experimental data indicates that RAGE is a critical mediator of the type 2 inflammatory reactions which drive the development of T2-hi AAD. However, clinical studies demonstrate that increased RAGE ligands and signaling strongly correlate with asthma severity, especially in severe neutrophilic asthma. This review presents an overview of the current understandings of RAGE in asthma pathogenesis, its role as a biomarker of disease, and future implications for mechanistic studies, and potential therapeutic intervention strategies.     

Concurrent cross‐reactivity of microbiota‐derived epitopes to both self and pathogens may underlie the “Hygiene hypothesis”

The current iteration of the “Hygiene hypothesis” proposes precipitous decline in exposure to conserved microbial products and metabolites in individuals in developed countries undermines innate self‐nonself “training” of immune system leading to allergy and autoimmunity. However, lack of innate “training” alone fails to account for the antigen‐driven nature of these immunopathologies. Here, we advance an alternative, antigen‐specific interpretive framework, SPIRAL (Specific ImmunoRegulatory Algorithm) that predicts “loss” of commensal microbiota‐derived epitopes cross‐reactive to both self and pathogens, rather than conserved microbial moieties or metabolites, underlies the “Hygiene hypothesis.” By mechanistically delineating how loss of selective microbiota in predisposed individuals could lead to corresponding “holes” in the epitope‐specific Foxp3⁺ regulatory T cell repertoire and subsequent selective immunopathologies, SPIRAL represents a novel interpretation of cross‐reactivity that could enable targeted discovery of microbiota species and their associated Treg epitopes “missing” in the diseases “Hygiene hypothesis” implicates, and provides a roadmap for a novel unified interpretation of self‐nonself discrimination and T helper phenotype selection.     

Adherence in severe asthma

Adherence in asthma is an important cause for concern. Although nearly 50% of asthma patients are considered poorly adherent to therapeutic advices, adherence is still difficult to assess, understand and improve despite major medical consequences. In this review, we revisited the literature of the last 10 years related to adherence in severe asthma. The concepts have changed and “compliance” is usually replaced by “adherence”. Assessment of adherence is addressing ethical issues, but provides important insight into difficult‐to‐treat asthma. Different tools have been used but none is routinely recommended. Health‐related outcomes (poor control, exacerbations, hospitalizations, lung function decline), which are clearly associated with severe asthma, are often worsened by non‐adherence with consequences also on patient related outcomes (quality of life). The potential behaviour associated with non‐adherence and all other related factors including easy‐to‐recognize psychological traits can help for patient's future management. Therapeutic educational interventions have been recognized with a scientifically proven efficiency even though evolution and improvements are needed. A multidisciplinary approach is required in severe asthma. Therapeutic adherence for a given patient is always a prerequisite to any other aspects when addressing severe asthma phenotypes. Severe asthma should be considered only in those who still experienced poor asthma outcomes despite optimal adherence. At a glance, poor adherence and severe asthma should be considered antinomic. Better understanding of the causes and customised management are potential future directions.     

Anti‐Asthma Simplified Herbal Medicine Intervention‐induced long‐lasting tolerance to allergen exposure in an asthma model is interferon‐γ, but not transforming growth factor‐β dependent

Background Chronic allergic asthma is the result of a T‐helper type 2 (Th2)‐biased immune status. Current asthma therapies control symptoms in some patients, but a long‐lasting therapy has not been established. Anti‐Asthma Simplified Herbal Medicine Intervention (ASHMI^?), a Chinese herbal formula improved symptoms and lung function, and reduced Th2 responses in a controlled trial of patients with persistent moderate to severe asthma. Objective We evaluated the persistence of ASHMI^? beneficial effects following therapy in a murine model of chronic asthma and the immunological mechanisms underlying such effects. Methods BALB/c mice sensitized intraperitoneally with ovalbumin (OVA) received 3 weekly intratracheal OVA challenges to induce airway hyper‐reactivity (AHR) and inflammation (OVA mice). Additionally, OVA mice were treated with ASHMI^? (OVA/ASHMI^?) or water (OVA/sham) for 4 weeks, and then challenged immediately and 8 weeks post‐therapy. In other experiments, OVA mice received ASHMI^? treatment with concomitant neutralization of IFN‐γ or TGF‐β. Effects on airway responses, cytokine‐ and OVA‐specific IgE levels were determined 8 weeks post‐therapy. Results Before treatment, OVA mice exhibited AHR and pulmonary eosinophilic inflammation following OVA challenge, which was almost completely resolved immediately after completing treatment with ASHMI^? and did not re‐occur following OVA re‐challenge up to 8 weeks post‐therapy. Decreased allergen‐specific IgE and Th2 cytokine levels, and increased IFN‐γ levels also persisted at least 8 weeks post‐therapy. ASHMI^? effects were eliminated by the neutralization of IFN‐γ, but not TGF‐β, during therapy. Conclusion ASHMI^? induced long‐lasting post‐therapy tolerance to antigen‐induced inflammation and AHR. IFN‐γ is a critical factor in ASHMI^? effects. Cite this as: K. Srivastava, T. Zhang, N. Yang, H. Sampson and X. M. Li, Clinical & Experimental Allergy, 2010 (40) 1678–1688.     

Daily allergic multimorbidity in rhinitis using mobile technology: A novel concept of the MASK study

Background

Multimorbidity in allergic airway diseases is well known, but no data exist about the daily dynamics of symptoms and their impact on work. To better understand this, we aimed to assess the presence and control of daily allergic multimorbidity (asthma, conjunctivitis, rhinitis) and its impact on work productivity using a mobile technology, the Allergy Diary.

Methods

We undertook a 1‐year prospective observational study in which 4 210 users and 32 585 days were monitored in 19 countries. Five visual analogue scales (VAS) assessed the daily burden of the disease (i.e., global evaluation, nose, eyes, asthma and work). Visual analogue scale levels <20/100 were categorized as “Low” burden and VAS levels ≥50/100 as “High” burden.

Results

Visual analogue scales global measured levels assessing the global control of the allergic disease were significantly associated with allergic multimorbidity. Eight hypothesis‐driven patterns were defined based on “Low” and “High” VAS levels. There were <0.2% days of Rhinitis Low and Asthma High or Conjunctivitis High patterns. There were 5.9% days with a Rhinitis High—Asthma Low pattern. There were 1.7% days with a Rhinitis High—Asthma High—Conjunctivitis Low pattern. A novel Rhinitis High—Asthma High—Conjunctivitis High pattern was identified in 2.9% days and had the greatest impact on uncontrolled VAS global measured and impaired work productivity. Work productivity was significantly correlated with VAS global measured levels.

Conclusions

In a novel approach examining daily symptoms with mobile technology, we found considerable intra‐individual variability of allergic multimorbidity including a previously unrecognized extreme pattern of uncontrolled multimorbidity.

     

Ambient particulate matter induces an exacerbation of airway inflammation in experimental asthma: role of interleukin‐33

High levels of ambient environmental particulate matter (PM10 i.e. < 10 μm median aerodynamic diameter) have been linked to acute exacerbations of asthma. We examined the effects of delivering a single dose of Sydney PM10 by intranasal instillation to BALB/c mice that had been sensitized to ovalbumin and challenged repeatedly with a low (≈3 mg/m³) mass concentration of aerosolized ovalbumin for 4 weeks. Responses were compared to animals administered carbon black as a negative control, or a moderate (≈30 mg/m³) concentration of ovalbumin to simulate an allergen‐induced acute exacerbation of airway inflammation. Delivery of PM10 to mice, in which experimental mild chronic asthma had previously been established, elicited characteristic features of enhanced allergic inflammation of the airways, including eosinophil and neutrophil recruitment, similar to that in the allergen‐induced exacerbation. In parallel, there was increased expression of mRNA for interleukin (IL)‐33 in airway tissues and an increased concentration of IL‐33 in bronchoalveolar lavage fluid. Administration of a monoclonal neutralizing anti‐mouse IL‐33 antibody prior to delivery of particulates significantly suppressed the inflammatory response induced by Sydney PM10, as well as the levels of associated proinflammatory cytokines in lavage fluid. We conclude that IL‐33 plays a key role in driving airway inflammation in this novel experimental model of an acute exacerbation of chronic allergic asthma induced by exposure to PM10.     

Macrophages—common culprit in obesity and asthma

Macrophages are essential innate immune cells that also regulate local metabolism. Endogenous or exogenous stimuli may polarize macrophages toward phenotypes that serve distinct innate immunological metabolic functions. IFN‐γ or lipopolysaccharide (LPS) polarizes macrophages toward the M1, or “classically activated” phenotype that participates in defense against intracellular pathogens. IL‐4, IL‐13, or chitin polarizes macrophages toward the M2, or “alternatively activated” phenotype, which defends against multicellular nematodes and fungi. As macrophages polarize in local environments, M1 and M2 macrophages may coexist in different organs and may differentially affect asthma and obesity, two comorbid diseases where polarized macrophages contribute to their pathogenesis. While M1 macrophages are considered beneficial in asthma and contribute to the pathology of obesity, M2 macrophages contribute to the pathology of asthma, but limit metabolic syndrome associated with obesity. Here, we discuss the roles for M1 and M2 macrophages in asthma and obesity, and propose a model by which M1‐mediated inflammation in adipose tissue enhances M2‐mediated inflammation in the asthmatic lung.     

Budesonide/formoterol for maintenance and reliever therapy in the management of moderate to severe asthma

The Global Initiative for Asthma (GINA) guidelines aim at improving asthma control and preventing future risk. For patients with moderate to severe asthma an inhaled corticosteroid (ICS) or an ICS/long‐acting β₂‐agonist (LABA) combination with a short‐acting β₂‐agonist (SABA) as reliever is recommended. Despite the availability of effective maintenance therapies, a large proportion of patients still fail to achieve guideline‐defined asthma control, and overuse of SABA reliever medication at the expense of ICS is commonly observed. New simplified treatment approaches may offer a solution and assist physicians to achieve overall asthma control. One such treatment approach, which is recommended in the GINA guidelines, is budesonide/formoterol for both maintenance and reliever therapy. This treatment strategy significantly reduces the rate of severe asthma exacerbations compared with ICS/LABA plus SABA and achieves equivalent daily symptom control compared with higher doses of ICS/LABA plus separate SABA for relief. These benefits are achieved at a lower overall steroid load, and budesonide/formoterol maintenance and reliever therapy is well tolerated in patients with moderate to severe asthma. This review discusses current asthma management in patients with moderate to severe disease and examines the evidence for alternative asthma management approaches.     

Comparing biologicals and small molecule drug therapies for chronic respiratory diseases: An EAACI Taskforce on Immunopharmacology position paper

Chronic airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), together with their comorbidities, bear a significant burden on public health. Increased appreciation of molecular networks underlying inflammatory airway disease needs to be translated into new therapies for distinct phenotypes not controlled by current treatment regimens. On the other hand, development of new safe and effective therapies for such respiratory diseases is an arduous and expensive process. Antibody‐based (biological) therapies are successful in treating certain respiratory conditions not controlled by standard therapies such as severe allergic and refractory eosinophilic severe asthma, while in other inflammatory respiratory diseases, such as COPD, biologicals are having a more limited impact. Small molecule drug (SMD)‐based therapies represent an active field in pharmaceutical research and development. SMDs expand biologicals’ therapeutic targets by reaching the intracellular compartment by delivery as either an oral or topically based formulation, offering both convenience and lower costs. Aim of this review was to compare and contrast the distinct pharmacological properties and clinical applications of SMDs‐ and antibody‐based treatment strategies, their limitations and challenges, in order to highlight how they should be integrated for their optimal utilization and to fill the critical gaps in current treatment for these chronic inflammatory respiratory diseases.