Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes.

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes. GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting ß2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS-formoterol reduces severe exacerbations by ⩾60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA. Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS-formoterol (maintenance-and-reliever therapy, "MART") in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting ß2-agonist (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11 years, new treatment options are added at Steps 3-4. Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.

Early priming of asthma and respiratory allergies: Future aspects of prevention: A statement by the European Forum for Education and Research in Allergy and Airway Disease (EUFOREA) and the EAACI-Clemens von Pirquet Foundation.

In order to summarize recent research on the prevention of allergies-particularly asthma-and stimulate new activities for future initiatives, a virtual workshop sponsored by the EAACI Clemens von Pirquet foundation and EUFOREA was held in October 2021. The determinants of the "allergic march" as well as the key messages from intervention studies were reviewed by an international faculty of experts. Several unmet needs were identified, and a number of priorities for future studies were proposed.

Healthy diet associated with better asthma outcomes in elderly women of the French Asthma-E3N study.

PURPOSE: The impact of a healthy diet on asthma prevention and management, particularly among elderly women, remains poorly understood. We investigated whether a healthy diet would be associated with fewer asthma symptoms, and, among women with asthma, with reduced uncontrolled asthma and metabolic-related multimorbidity. METHODS: We included 12,991 elderly women (mean age = 63 years) from the Asthma-E3N study, a nested case-control study within the French E3N cohort. Negative binomial regressions were used to analyse associations between a healthy diet [evaluated by the Alternate Healthy Eating Index-2010 (AHEI-2010)] and a validated asthma symptom score, and logistic regressions to analyse associations between the AHEI-2010 with the asthma control test and multimorbidity profiles previously identified by clustering methods on medications used. RESULTS: After adjustment for potential confounders, a linear inverse association was found between the AHEI-2010 score and the asthma symptom score [mean score ratio (95% CI) = 0.82 (0.75-0.90) for the highest versus lowest quintile; p for trend < 0.0001]. In addition, women in the highest versus lowest AHEI-2010 tertile were at a lower risk to belong to the "Predominantly metabolic multimorbidity-related medications profile" compared to the "Few multimorbidity-related medications" profile [OR 0.80 (0.63-1.00) for tertile 3; p for trend = 0.05; n = 3474]. CONCLUSION: Our results show that a healthy dietary intake could play an important role in the prevention and management of asthma over the life course.

Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes.

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes. GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting ß2 -agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS-formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA. Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS-formoterol (maintenance-and-reliever therapy, "MART") in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting ß2 -agonist (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11 years, new treatment options are added at Steps 3-4. Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.

Maternal microbiome regulation prevents early allergic airway diseases in mouse offspring.

BACKGROUND: Asthma is a serious global health problem, severely affecting the lives of sufferers and their families. An exceptionally hygienic home and reduced microbial exposure can aggravate the incidence of childhood asthma. METHODS: Specific-pathogen-free BALB/c mice were pre-treated with bacterial lysate (BL; 1 mg/kg) as a high microbial load maternal mouse model, and then, the offspring mice were established as an allergic airway disease (AAD) model. The expression levels of TLR2, TLR4, and HDAC9 in the mother's intestine and the offspring's lungs were detected. Relevant indicators of regulatory T cells (Tregs) were identified in the mother and offspring mice. The changes in the expression of Th1-, Th2-, Th9-, and Th17-related cytokines in the offspring mice were evaluated among different pre-treated groups. RESULTS: After augmenting the mothers' intestinal microbiota through oral BL gavage, the expression of TLR2 and TLR4 in the colon mucosa and colon lymphoid tissues was enhanced and that of HDAC9 in the colon mucosa was decreased, and the proportion of spleen Tregs was increased. The offspring showed similar changes in the AAD model compared with the offspring of the control-group mothers: TLR2 and TLR4 expression in the lungs and the proportion of spleen Tregs increased, HDAC9 expression in the lungs decreased, and AAD-induced airway pathologic characteristics were reversed; additionally, Th1/Th2 and Th9 imbalances were rectified. CONCLUSIONS: This study presents a new framework for the prevention of childhood asthma, elucidating the mechanism of regulating the mother's intestinal microbiome to protect the offspring's early asthma via animal experiments.

Asthma control and quality of life in a real-life setting: a cross-sectional study of adult asthma patients in Japan (ACQUIRE-2).

Objective: The level of asthma control in adult asthma patients receiving treatment in clinical practice from allergy and/or respiratory specialists in Japan remains unclear. We conducted the ACQUIRE-2 study (NCT02640742) to evaluate level of asthma control, asthma symptoms, health-related quality of life (HR-QoL), and reliever medication use in this setting. Methods: This observational study was undertaken between December 2015 and June 2016 in 58 medical institutions across Japan. We enrolled outpatients aged ≥20 years diagnosed with asthma for ≥1 year who were being managed by specialists. Criteria to evaluate the level of asthma control were based on modified definitions of the Asthma Prevention and Management Guideline 2015, Japan (JGL 2015) and Global Initiative for Asthma (GINA) 2012. Asthma symptoms, HR-QoL, and reliever medication use were also evaluated. Results: Of 1250 enrolled patients, 1175 were analyzed, 62.9% of whom were women. Mean (± standard deviation) age and duration of asthma were 59.7 ± 14.5 years and 16.9 ± 14.0 years, respectively. Using JGL 2015-based criteria, 24.4%, 69.2%, and 6.5% of patients had well-controlled, insufficiently-controlled, and poorly-controlled asthma, respectively. Using GINA-based criteria, 35.1%, 49.8%, and 15.1% of patients had controlled, partly controlled, and uncontrolled asthma, respectively. Daytime and nighttime asthma symptoms were experienced by 51.5% and 44.9% of patients, respectively. The mean MiniAQLQ score was 5.8 ± 1.0 (7-point scale). Conclusions: Asthma was not well-controlled in the majority of patients in this study. To achieve better asthma control, improvements in symptom monitoring and management may be required.

Is Allergen Immunotherapy in Children Disease Modifying? A Review of the Evidence.

PURPOSE OF REVIEW: Although evidence supports a beneficial effect of allergen immunotherapy on the symptoms of allergic respiratory disease and food allergy, it is not clear whether immunotherapy modifies the natural history of these conditions. RECENT FINDINGS: In aeroallergen immunotherapy, studies suggest that prevention of asthma can be attained. Less evident is the ability of immunotherapy to prevent new allergen sensitizations and more studies are needed to test whether immunotherapy can continue suppressing airway symptoms after treatment discontinuation. In food allergen immunotherapy, there is evidence that unresponsiveness to a food challenge can be sustained in some treatment recipients, but little knowledge exists as to the dose and duration of treatment that can optimize this effect. Suggestive evidence exists that allergen immunotherapy can modify allergic disease in children, but definitive studies are lacking. More research in the field is required.

Recommendations for the prevention and diagnosis of asthma in children: Evidence from international guidelines adapted for Mexico.

BACKGROUND: With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. METHODS: The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. RESULTS: The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. CONCLUSIONS: For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma.

Effective treatment of allergic airway inflammation with Helicobacter pylori immunomodulators requires BATF3-dependent dendritic cells and IL-10.

The prevalence of allergic asthma and other atopic diseases has reached epidemic proportions in large parts of the developed world. The gradual loss of the human indigenous microbiota has been held responsible for this trend. The bacterial pathogen Helicobacter pylori is a constituent of the normal gastric microbiota whose presence has been inversely linked to allergy and asthma in humans and experimental models. Here we show that oral or i.p. tolerization with H. pylori extract prevents the airway hyperresponsiveness, bronchoalveolar eosinophilia, pulmonary inflammation, and Th2 cytokine production that are hallmarks of allergen-induced asthma in mice. Asthma protection is not conferred by extracts from other enteropathogens and requires a heat-sensitive H. pylori component and the DC-intrinsic production of IL-10. The basic leucine zipper ATF-like 3 (BATF3)-dependent CD103(+)CD11b(-) dendritic cell lineage is enriched in the lungs of protected mice and strictly required for protection. Two H. pylori persistence determinants, the γ-glutamyl-transpeptidase GGT and the vacuolating cytotoxin VacA, are required and sufficient for asthma protection and can be administered in purified form to prevent asthma. In conclusion, we provide preclinical evidence for the concept that the immunomodulatory properties of H. pylori can be exploited for tolerization strategies aiming to prevent allergen-induced asthma.

Revisiting the hygiene hypothesis for allergy and asthma.

The hygiene hypothesis, which describes the protective influence of microbial exposures in early life on the development of allergy and asthma, has continued its swell of academic interest, investigation, and evolution. This article is focused on studies published in the past 3 years that have furthered the substance and shape of hygiene theory, primarily as it relates to allergic airways and asthma. Recent investigations have furthered an overarching "microbiome hypothesis" to home features, medical practices, and cleanliness behaviors that are suspects in the hygiene effect. Relatively crude markers of the protective microbial environment have been supplanted by culture-independent microbiome science, distinguishing the characteristics of potentially protective microbiomes from pathologic features. Understanding how the microbiome is shaped and affects healthful versus harmful outcomes in the human host is relatively nascent. Good clues are emerging that give mechanistic substance to the theory and could help guide microbe-based therapeutics to fill the allergy and asthma management gap in prevention and disease modification.

Neutrophils in respiratory syncytial virus infection: A target for asthma prevention.

Lower respiratory tract infections by respiratory syncytial virus (RSV) are the foremost cause of infant hospitalization and are implicated in lasting pulmonary impairment and the development of asthma. Neutrophils infiltrate the airways of pediatric patients with RSV-induced bronchiolitis in vast numbers: approximately 80% of infiltrated cells are neutrophils. However, why neutrophils are recruited to the site of viral respiratory tract infection is not clear. In this review we discuss the beneficial and pathologic contributions of neutrophils to the immune response against RSV infection. Neutrophils can limit viral replication and spread, as well as stimulate an effective antiviral adaptive immune response. However, low specificity of neutrophil antimicrobial armaments allows for collateral tissue damage. Neutrophil-induced injury to the airways during the delicate period of infant lung development has lasting adverse consequences for pulmonary architecture and might promote the onset of asthma in susceptible subjects. We suggest that pharmacologic modulation of neutrophils should be explored as a viable future therapy for severe RSV-induced bronchiolitis and thereby prevent the inception of subsequent asthma. The antiviral functions of neutrophils suggest that targeting of neutrophils in patients with RSV-induced bronchiolitis is best performed under the umbrella of antiviral treatment.

Association of Small Airway Functional Indices With Respiratory Symptoms and Comorbidity in Asthmatics: A National Cross-Sectional Study.

Background: Small airway dysfunction (SAD) and airway inflammation are vital in asthma exacerbations. Type 2 inflammation (T2), mediated by cytokines from T helper 2 cell (Th2) such as interleukin (IL)-4, IL-5, and IL-13, is a potential mechanism underlying SAD. Research on small airway function in asthma is limited. We aimed to explore the correlation between small airway function and respiratory symptoms and comorbidity in T2 and non-T2 asthma. Methods: Derived from the National Health and Nutrition Examination Survey (NHANES), our study encompassed 2,420 asthma patients aged 6 - 79 years, including pulmonary function (PF) data such as forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75), forced expiratory volume in 1 second (FEV1), forced expiratory volume in 3 seconds (FEV3), forced expiratory volume in 6 seconds (FEV6), and forced vital capacity (FVC). To evaluate the small airway function, we calculated z-scores for FEF25-75, FEF25-75/FVC, FEV1/FEV6, and FEV3/FEV6. Logistic regression determined the adjusted odds ratios (aORs) for symptoms and comorbidity. Results: FEF25-75, FEV1/FEV6, and FEV3/FEV6 correlated with asthmatic symptoms. FEF25-75 had the strongest association with wheezing or whistling attacks. An increase of 1 standard deviations (SD) in FEF25-75 reduced recurrent wheezing (aOR: 0.70; 95% confidence intervals (95% CIs): 0.65 - 0.76) and severe attacks (aOR: 0.67; 95% CI: 0.62 - 0.94). These indices were also linked to dry cough and hay fever, particularly FEV3/FEV6 reducing hay fever risk (aOR: 0.70; 95% CI: 0.55 - 0.91) in non-T2 asthma. FEF25-75/FVC related to persistent (aOR: 0.78; 95% CI: 0.72 - 0.84) and severe attacks (aOR: 1.14; 95% CI: 1.08 - 1.22) in non-T2 groups. Lower indices combined with T2 exposure raised severe attack risk. Conclusions: In this nationwide study, small airway function correlated with symptom onset, especially in T2 asthma. Small airway injury differed between T2 and non-T2 asthma. Prospective research is needed to establish reference values.

Global Initiative for Asthma Strategy 2021: Executive Summary and Rationale for Key Changes.

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes. GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting ß2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS-formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA. Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS-formoterol (maintenance-and-reliever therapy, "MART") in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting ß2-agonist (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11 years, new treatment options are added at Steps 3-4. Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.

Comprehensive In-Patient Education Consult for Asthma Exacerbations.

BACKGROUND: Asthma is the most common chronic disease leading to hospital admissions and readmissions in childhood. Bedside nurses and respiratory therapists are the primary asthma educators, but they may lack time or knowledge to provide comprehensive asthma education and identify barriers to care. Patients and their parent(s) may benefit from comprehensive education and assessment of barriers from a certified asthma educator. METHODS: A team of certified asthma educators used a quality improvement method to create an in-patient asthma education consulting service. The in-patient pulmonary consult and medical teams referred subjects ≥ 1 y in age with a new or existing diagnosis of asthma who had been admitted to the ICU or identified as having concerns for poor medication adherence to the asthma consult. The asthma consult provided face-to-face education with the subject and parent(s), addressed barriers to the plan of care, and helped facilitate appointments to an asthma specialist after discharge. RESULTS: There were 126 subjects eligible for the asthma consult pilot implemented October 1, 2018-April 30, 2020. The asthma consult saw 52 subjects. Subjects who received consults had a higher rate of previous health care utilization and existing specialist for asthma. After the in-patient stay, the odds of returning to the emergency department/urgent care (UC) or hospital within the following 12 months did not differ between asthma consult and control group. However, after adjusting for covariates of age, race, ethnicity, previous health care utilization, and existing specialist, there was a significant difference in the odds of readmission and revisits (adjusted odds ratio 0.39 [95% CI 0.16-0.98], P = .04) for the asthma consult group compared to the control group. CONCLUSIONS: Providing comprehensive, face-to-face asthma education and working with subjects and their parent(s) to address barriers to medication adherence and facilitate specialty follow-up post discharge decreased health care utilization.

Global Initiative for Asthma Strategy 2021. Executive Summary and Rationale for Key Changes.

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes. GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting ß2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS-formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function, and inflammatory outcomes as daily ICS plus as-needed SABA. Key changes in GINA 2021 include division of the treatment figure for adults and adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS-formoterol (maintenance-and-reliever therapy, "MART") in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting ß2-agonist (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11 years, new treatment options are added at Steps 3-4. Across all age groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment, and review remain essential to optimize asthma outcomes.

Plant-Based Diets and the Incidence of Asthma Symptoms among Elderly Women, and the Mediating Role of Body Mass Index.

We aimed to test the hypothesis that adherence to a healthful plant-based diet (hPDI) is associated with a subsequent decrease in the incidence of asthma symptoms, with an opposite association with adherence to an unhealthful plant-based diet (uPDI). In addition, we evaluated a potential mediating role of body mass index (BMI) and the modifying effect of smoking. Among 5700 elderly women from the French Asthma-E3N study with dietary data in 1993 and 2005, we assessed the incidence of asthma symptoms in 2018 among women with no asthma symptoms in 2011. BMI was evaluated in 2008. Mediation analyses in the counterfactual framework were used to disentangle total, direct, and indirect effects mediated by BMI. We found that both healthful and unhealthful plant-based diets were associated with a lower incidence of asthma symptoms over time, mediated by BMI (OR (95%CI) for the indirect effect: 0.94 (0.89-1.00) for hPDI and 0.92 (0.70-1.00) for uPDI)). Associations with both healthful and unhealthful PDIs were mediated by changes in BMI by 33% and 89%, respectively. Plant-based diets (healthful and unhealthful) were associated with subsequently reduced incidences of asthma symptoms over time, partly or almost totally mediated by BMI according to their nutritional quality.