Rationale In the nation-wide, multi-centre CARE4ALL study (NCT05440097), GINA based physician training improve asthma care and asthma symptom control. Here we examined the potential risk factors associated with not achieving well-controlled asthma after the 48-week intervention. Methods Patients were categorised into the “well-controlled” (Asthma Control Questionnaire-5 [ACQ-5]) <0.75) or “not well-controlled” (ACQ-5≥0.75) groups based on ACQ-5 at week 48. Association analyses were exploited for the effect of baseline demographics, asthma history and clinical characteristics on asthma control level. Multiple logistic regression and stepwise regression was utilized to identify risk factors for unsatisfactory asthma control at week 48. Results Among the 1132 patients with week-48 ACQ-5 data, 641 had well-controlled asthma and 491 did not. Notable demographic differences between the two groups included younger age (mean 46.5 vs 52.0 years, p<0.0001) and less occupational exposure to dust, allergens or harmful gases (5.3% vs 12.2%, p<0.0001) in the “well-controlled” group. The “well-controlled” group had shorter asthma duration (median 37.1 vs 63.2 months, p<0.0001), fewer asthma exacerbations in the 1 year preceding baseline (29.3% vs 35.0%, p=0.0412), and better baseline lung function and health related quality-of-life. Higher percentages of patients in the “well-controlled” group were receiving inhaled corticosteroid (ICS)-containing medications at baseline (44.3% vs 38.5%, p=0.0213) and showed good adherence when assessed at week 48 (43.1% vs 40.1%, p=0.0006). Multiple logistic regression identified (Table 1): older age (odds ratio [OR] 1.031; 95% confidence interval [95% CI] 1.009-1.053); occupational exposure to dust, allergens or harmful gases for 3 months (OR 2.402; 95% CI 1.042-5.539); residing in rural villages (OR 1.919; 95% CI 1.102-3.340); and not showing good adherence at week 48 (OR 1.824; 95% CI 1.069-3.112) as being associated with not achieving well-controlled asthma at week 48. Higher baseline FEV1%pred was identified as a protective factor (OR 0.987; 95% CI 0.975-0.999). Conclusions Among patients enrolled in this QIP, older age, occupational exposure, rural residency, and lower FEV1%pred at baseline were associated with not achieving well-controlled asthma, suggesting special attention in managing asthma patients with these characteristics. Additionally, good adherence is a key factor for achieving good asthma control.

Rationale To improve asthma management and patient outcomes, the CARE4ALL study (NCT05440097) conducted a nationwide multifaceted quality improvement programme (QIP) in China. It aimed to standardize asthma care based on Global Initiative for Asthma (GINA) recommendations. Methods Patients aged ≥14 years with diagnosed asthma were recruited from 31 tertiary or secondary hospitals across mainland China. GINA based education targeting pulmonologists and specialist nurses, consisting of initial comprehensive education and subsequent regular reinforcement sessions was provided. Patients were followed-up for 48 weeks at 12-week intervals. The primary endpoint was change from baseline in the proportion of patients using inhaled corticosteroid (ICS)-based maintenance and/or relieving treatment at Week 48. Key secondary and exploratory endpoints included change in Asthma Control Questionnaire-5 (ACQ-5) and Asthma Quality of Life Questionnaire (Standardised) for ≥12 years (AQLQ(S)+12). Results 1500 patients were enrolled, and 1362 constituted the full analysis set (patients with at least one non-missing post-intervention assessment). By-visit results are summarized in Table 1. The proportion of patients using ICS-based medication increased by 13.1% (95% CI 9.3%-16.9%), from 41.9% at baseline to 55.0% at week 48 (odds ratio=1.761, 95% CI 1.497-2.072, p<0.0001). At week 48, 56.6% of patients had well controlled asthma (ACQ-5≤0.75), substantially higher than the 26.1% at baseline, while 23.8% and 19.6% of patients had partly controlled asthma (0.75

Spirometry is used to determine what is "unusual" lung function compared with what is "usual" for healthy non-smokers. This study aimed to investigate regional variation in the forced vital capacity (FVC) and in the forced expiratory volume in one second to FVC ratio (FEV1/FVC) using cross-sectional data from all 41 sites of the multinational Burden of Obstructive Lung Disease study. Participants (5,368 men; 9,649 women), aged >= 40 years, had performed spirometry, had never smoked and reported no respiratory symptoms or diagnoses. To identify regions with similar FVC, we conducted a principal component analysis (PCA) on FVC with age, age2 and height2, separately for men and women. We regressed FVC against age, age2 and height2, and FEV1/FVC against age and height2, for each sex and site, stratified by region. Mean age was 54 years (both sexes), and mean height was 1.69 m (men) and 1.61 m (women). The PCA suggested four regions: 1) Europe and richer countries; 2) the Near East; 3) Africa; and 4) the Far East. For the FVC, there was little variation in the coefficients for age, or age2, but considerable variation in the constant (men: 2.97 L in the Far East to 4.08 L in Europe; women: 2.44 L in the Far East to 3.24 L in Europe) and the coefficient for height2. Regional differences in the constant and coefficients for FEV1/FVC were minimal (<1%). The relation of FVC with age, sex and height varies across and within regions. The same is not true for the FEV1/FVC ratio.

Introduction We investigated whether the forced expiratory volume in 6 s (FEV6) can be used as a surrogate for the forced vital capacity (FVC).Methods The Burden of Obstructive Lung Disease is a multinational cohort study. At baseline, data were collected from adults, aged 40 years or older, from 41 sites across 34 countries. Participants from 18 sites were followed-up after a median of 8.3 years. Participants who completed the study core questionnaire and had acceptable post-bronchodilator spirometry were included. We performed receiver operating characteristic analyses to measure the ability of FEV1/FEV6 less than the lower limit of normal (LLN) to correctly classify FEV1/FVC less than the LLN, and FEV6 less than the LLN to correctly classify FVC less than the LLN. We used multilevel regression analyses to assess the association of discordant measurements with respiratory symptoms, quality of life and lung function decline.Results At baseline, 28 604 participants were included. 53% were female (15 060). 10% (2876) had chronic airflow obstruction for FEV1/FVC, compared with 9% (2704) for FEV1/FEV6. 37% (10 637) had spirometric restriction for FVC, compared with 35% (9978) for FEV6. The FEV1/FEV6 had excellent accuracy in identifying FEV1/FVC less than the LLN (area under the curve (AUC): 0.90, 95% CI, 0.89 to 0.91, κ coefficient 0.82). The FEV6 also had excellent agreement in identifying FVC less than the LLN (AUC: 0.95, 95% CI, 0.94 to 0.95, κ coefficient 0.90). Discordant reductions in FEV1/FEV6 (1%, 345) and FEV6 (1%, 309) were associated with greater odds of having respiratory symptoms and a lower physical quality of life. 3870 participants were followed up. Those with discordant reductions in FEV1/FEV6 and FEV6 were more likely to have chronic airflow obstruction and spirometric restriction at follow-up.Conclusions There is strong agreement between the FVC and FEV6 in the identification of chronic airflow obstruction and spirometric restriction.

In Australia, short-acting β2-agonists (SABA) are available both over the counter (OTC) and on prescription. This ease of access may impact SABA use in the Australian population. Our aim was to assess patterns and outcome associations of prescribed, acquired OTC and reported use of SABA by Australians with asthma. This was a cross-sectional study, using data derived from primary care electronic medical records (EMRs) and patient completed questionnaires within Optimum Patient Care Research Database Australia (OPCRDA). A total of 720 individuals aged ≥ 12 years with an asthma diagnosis in their EMRs and receiving asthma therapy were included. The annual number of SABA inhalers authorised on prescription, acquired OTC and reported, and the association with self-reported exacerbations and asthma control were investigated. 92.9

BackgroundTraining primary care doctors and nurses to use Practical Approach to Care Kit (PACK) improved management of asthma and chronic obstructive pulmonary disease (COPD) in a previous randomised trial. The present study examined the training effects including a second year of follow-up with expanded coverage of repeated training sessions.MethodsUsing a stepped-wedge cluster randomised trial design, 48 clinics were randomly allocated either to sequence A: (1) no intervention, (2) no intervention, (3) intervention or sequence B: (1) no intervention, (2) intervention, (3) intervention, during three 12-month periods. Primary outcomes were change in treatment and spirometry ordering. Effects of any exposure to the training, and of exposure to the first and second years of training, were estimated with mixed effect logistic regression models.ResultsAny exposure to training was associated with increased changes in treatment (OR adjusted for calendar time (OR) 1.29, 95% CI 1.02 to 1.64) and more spirometry ordering (OR 1.55, (95% CI 1.22 to 1.97)) in asthma patients, and with more spirometry ordering (OR 1.50 (95% CI 1.15 to 1.96)) in patients with COPD. Change in asthma treatment was more likely during the first and second year of exposure to training compared with no exposure (ORs 1.43 (95% CI 1.09 to 1.87); 1.91 (95% CI 1.21 to 3.02)), respectively. Spirometry was more likely during the first and second year of exposure in asthma patients (ORs 1.76 (95% CI 1.34 to 2.30); 2.05 (95% CI 1.32 to 3.19)) and in patients with COPD (ORs 1.57 (95% CI 1.18 to 2.10)); 1.71 (95% CI 1.08 to 2.70)).ConclusionExtended follow-up suggested that PACK training continued to be effective in improving chronic respiratory care and that effective intervention delivery was sustainable for 2 years.Trial registration numberNCT02786030.

Background Hypersensitivity to house dust mite (HDM) allergens is a common cause of allergic asthma symptoms and can be effectively treated with allergy immunotherapy (AIT). Objective To investigate whether genetic and type 2 (T2) inflammatory biomarkers correlate with disease severity in subjects with allergic asthma, and whether this can be modified by AIT. Methods MITRA ( NCT01433523 ) was a phase III, randomised, double-blind, placebo-controlled trial of HDM sublingual immunotherapy (SLIT)-tablets in adults with HDM allergic asthma. Post hoc analyses of the study population (N=742) evaluated associations between T2 inflammatory (blood eosinophils, eosinophil cationic protein (ECP), total IgE and tryptase) and genetic (single-nucleotide polymorphisms, SNP) biomarkers (n=582) for the primary study endpoint (time to first moderate/severe asthma exacerbation). SNP associations were verified in HDM-positive subgroup from an independent 3-year Severe Asthma Research Programme (SARP3) subject cohort. Results An increased asthma exacerbation risk in subjects homozygous for SNP rs7216389 (chromosomal locus 17q12-21) was reduced (p = 0.037) by treatment with HDM SLIT (HR=0.37 (95% CI 0.22 to 0.64), p<0.001). The associations between exacerbation risk and 17q12-21 SNPs were replicated in the SARP3 HDM-positive subgroup. High levels of T2 biomarkers were associated with increased risk of asthma exacerbations in the placebo group. HDM SLIT-tablet treatment reduced this risk (blood eosinophils: HR=0.50 (95% CI 0.30 to 0.85); ECP: HR=0.45 (95% CI 0.29 to 0.87); tryptase: HR=0.45 (95% CI 0.25 to 0.80)). The treatment effect was higher (p = 0.006) for subjects with a higher number of elevated T2 biomarkers. Conclusions HDM SLIT-tablet AIT is efficacious in HDM-sensitised asthma subjects with a genetic asthma predisposition and/or an underlying T2 endotype. Trial registration number NCT01433523 .

The Global Initiative for Asthma (GINA) was established in 1993 by the World Health Organization and the US National Heart Lung and Blood Institute to improve asthma awareness, prevention and management worldwide. GINA develops and publishes evidence-based, annually updated resources for clinicians. GINA guidance is adopted by national asthma guidelines in many countries, adapted to fit local healthcare systems, practices, and resource availability. GINA is independent of industry, funded by the sale and licensing of its materials. This review summarizes key practical guidance for primary care from the 2022 GINA strategy report. It provides guidance on confirming the diagnosis of asthma using spirometry or peak expiratory flow. GINA recommends that all adults, adolescents and most children with asthma should receive inhaled corticosteroid (ICS)-containing therapy to reduce the risk of severe exacerbations, either taken regularly, or (for adults and adolescents with “mild” asthma) as combination ICS–formoterol taken as needed for symptom relief. For patients with moderate–severe asthma, the preferred regimen is maintenance-and-reliever therapy (MART) with ICS–formoterol. Asthma treatment is not “one size fits all”; GINA recommends individualized assessment, adjustment, and review of treatment. As many patients with difficult-to-treat or severe asthma are not referred early for specialist review, we provide updated guidance for primary care on diagnosis, further investigation, optimization and treatment of severe asthma across secondary and tertiary care. While the GINA strategy has global relevance, we recognize that there are special considerations for its adoption in low- and middle-income countries, particularly the current poor access to inhaled medications.

Climate change and its impacts on the health of our planet and its people are, deservedly, on centre stage in international discourse, and have prompted critical evaluation of all human activities that could lessen the degree and progression of these effects. Health care, too, is under scrutiny for its contribution to climate change. Among the many issues is the global warming potential of gases in medical devices, including fluorinated gas propellants in pressurised metered-dose inhalers (pMDIs) that are often used for the treatment of airway diseases; these contribute a small but substantial proportion of global greenhouse gas emissions (estimated as <0 center dot 1%). 1-9 Many countries, including the USA, the UK, and several in mainland Europe, have developed policies to reduce the carbon footprint of inhalers. The chief measures proposed are to replace harmful propellants, such as hydrofluoroalkane-134a and hydrofluoroalkane-227ea,1,2 with safer alternatives that are under development; 4,10,11 in the meantime to choose pMDIs that have lower fluorinated gas content;12 and to encourage a switch to dry-powder inhalers (DPIs), which do not contain propellants (assuming that the patient can use the relevant inhaler correctly).12,13 At the same time, international action is being taken to limit use of perfluoroalkyl and polyfluoroalkyl substances (PFAS),14 a large and diverse group of chemicals that are widely used in consumer products and industry, and some of which have significant toxicity and accumulate in the environment over time. Actions to limit PFAS, if worded too broadly, could affect supply of some new propellants that have low global warming potential and no evidence of toxicity or accumulation over time.

Asthma and chronic obstructive pulmonary disease (COPD) affect millions of people throughout Europe, being one of the leading causes of death in the continent. Both conditions also impose considerable morbidity on patients, adversely affecting individuals’ physical and psychological wellbeing, and their capacity to live and work normally. Asthma and COPD also impose a substantial economic burden on healthcare providers and wider society through both direct and indirect costs of care. Inhaler-delivered therapy has been central to the successful management of both conditions for several decades. Advances in device technology and understanding of the pathophysiology of both conditions (while theoretically introducing greater flexibility and responsiveness into the repertoire of inhalation therapies) have also added complexity and sometimes confusion into the task of identifying the precise combination of medication and delivery device best suited to the needs of individual patients. Recently published multinational consensus reports have set out best-practice frameworks for the management of both asthma and COPD. Presentations at the two symposia summarised in this report examined the implications of these guidelines for the treatment of both conditions. Special focus was on dry power inhalers (DPI) as a means of delivering effective treatment that combines ease of use and widespread acceptance among patients, with the potential to reduce medically-related emissions of greenhouses gases compared with pressurised metered-dose inhalers (pMDI). The authors emphasised the importance of patient partnership in determining the care plan, including the choice of both inhaler device and treatment; the benefits of regular monitoring of adherence to the treatment for both patients with asthma and COPD; and the benefits of simplicity, using one type of inhaler where possible to minimise critical errors in inhalation technique.

Background To gain a global perspective on short-acting β 2 -agonist (SABA) prescriptions and associated asthma-related clinical outcomes in patients with asthma, we assessed primary health data across 24 countries in five continents. Methods SABINA III was a cross-sectional study that employed electronic case report forms at a study visit (in primary or specialist care) to record prescribed medication(s), over-the-counter (OTC) SABA purchases and clinical outcomes in asthma patients (≥12 years old) during the past 12 months. In patients with ≥1 SABA prescriptions, associations of SABA with asthma symptom control and severe exacerbations were analysed using multivariable regression models. Results Of 8351 patients recruited (n=6872, specialists; n=1440, primary care), 76.5% had moderate-to-severe asthma and 45.4% experienced ≥1 severe exacerbations in the past 12 months. 38% of patients were prescribed ≥3 SABA canisters; 18.0% purchased OTC SABA, of whom 76.8% also received SABA prescriptions. Prescriptions of 3–5, 6–9, 10–12 and ≥13 SABA canisters ( versus 1–2) were associated with increasingly lower odds of controlled or partly controlled asthma (adjusted OR 0.64 (95% CI 0.53–0.78), 0.49 (95% CI 0.39–0.61), 0.42 (95% CI 0.34–0.51) and 0.33 (95% CI 0.25–0.45), respectively; n=4597) and higher severe exacerbation rates (adjusted incidence rate ratio 1.40 (95% CI 1.24–1.58), 1.52 (95% CI 1.33–1.74), 1.78 (95% CI 1.57–2.02) and 1.92 (95% CI 1.61–2.29), respectively; n=4612). Conclusions This study indicates an association between high SABA prescriptions and poor clinical outcomes across a broad range of countries, healthcare settings and asthma severities, providing support for initiatives to improve asthma morbidity by reducing SABA overreliance.

The use of a single inhaler containing the combination of an inhaled corticosteroid (ICS) and formoterol, a specific long-acting bronchodilator, for both maintenance and quick relief therapy (single maintenance and reliever therapy [SMART or MART]) is recommended by both the Global Initiative for Asthma and the National Asthma Education and Prevention Program Coordinating Committee in steps 3 and 4 of asthma management. This article provides practical advice about implementing SMART in clinical practice based on evidence and clinical experience. Fundamental to SMART is that ICS-formoterol provides quick relief of asthma symptoms similar to that of short-acting beta(2)-agonists such as albuterol, while reducing the risk for severe asthma exacerbations and at an overall lower ICS exposure. Most SMART clinical trials were in adults and adolescents (aged >= 12 years), using budesonide-formoterol 160/4.5 mu g (delivered dose), one inhalation once or twice daily (step 3) and two inhalations twice daily (step 4). For both steps 3 and 4, patients take additional inhalations of budesonide-formoterol 160/4.5 mu g, one inhalation whenever needed for symptom relief, up to a maximum for adults and adolescents of 12 total inhalations in any single day (delivering 54 mu g formoterol). The efficacy and safety of SMART with budesonide-formoterol and beclometasone-formoterol have been confirmed, but other ICS-long-acting bronchodilator combinations have not been studied. The SMART regimen should be introduced with a careful explanation of its role in self-management, preferably with a customized written asthma action plan. The cost to patients and the availability of SMART treatment will depend on the prescribed dose and national or local payer agreements. (C) 2021 American Academy of Allergy, Asthma & Immunology

BackgroundThe Global Initiative for Asthma report recommends consideration of add-on biologics for patients with type 2 inflammation (blood eosinophils ≥150 cells/μL, fractional exhaled nitric oxide [Feno] ≥20 parts per billion or allergic asthma) whose asthma cannot be controlled by high-dose inhaled corticosteroids. In QUEST (NCT02414854), add-on dupilumab versus placebo was efficacious in patients with uncontrolled, moderate to severe asthma, including those with eosinophils greater than or equal to 150 cells/μL and/or Feno greater than or equal to 25 parts per billion.ObjectiveTo assess dupilumab efficacy in patients with a type 2 phenotype in the presence or absence of allergic asthma phenotype.MethodsPatients aged 12 years or older received add-on dupilumab 200/300 mg versus matched placebo every 2 weeks for 52 weeks. Allergic asthma phenotype was defined as baseline serum total IgE greater than or equal to 30 IU/mL and 1 or more perennial aeroallergen-specific IgE level greater than or equal to 0.35 kU/L. Annualized rate of severe asthma exacerbations and changes from study baseline in prebronchodilator and postbronchodilator FEV1 were evaluated in patients with allergic and nonallergic phenotype with baseline blood eosinophils greater than or equal to 150 cells/μL and/or Feno greater than or equal to 20 parts per billion.ResultsOf 1902 patients in QUEST, 83.3% had eosinophils and/or Feno above Global Initiative for Asthma thresholds; 56.9% had evidence for allergic asthma. Dupilumab significantly reduced the rate of severe asthma exacerbations in patients with (48.8%) and without (64.0%) evidence of allergic asthma and improved prebronchodilator and postbronchodilator FEV1 in patients with elevated type 2 biomarkers, irrespective of whether they showed evidence of an allergic asthma phenotype.ConclusionsIn patients with type 2 biomarkers over Global Initiative for Asthma thresholds, dupilumab significantly reduced exacerbations and improved lung function. Efficacy was not impacted by allergic status.

Background: To evaluate the impact of training primary care physicians (PCPs) in the use of the practical approach lung health-global alliance against chronic respiratory diseases (PAL-GARD) upon their diagnostic skills. Methods: In this real-life three-phase study, PCPs were allocated to a PAL-GARD training or control group. Patients who sought a primary care health facility due to cough, dyspnea and/or wheezing were eligible. The clinical diagnoses made by PCPs during the baseline and post-intervention phase were audited by a panel of pulmonologists. Kappa inter-rater statistics was used to compare agreement between PCPs and pulmonologists. Results: Thirty PCPs evaluated 536 patients, 358 in the intervention and 178 in the control group. According to Kappa, there was an increase in the agreement in the diagnosis of asthma (from 0.546 to 0.638), tuberculosis (from 0.393 to 0.655) and acute respiratory infections (ARI) (from 0.577 to 0.584) was observed in the PAL-GARD group, but there was a reduction in chronic obstructive pulmonary disease (COPD) (from 0.430 to 0.284). Conclusions: In this setting, PAL-GARD-based guide and training improved the clinical diagnosis of common respiratory diseases with the exception of COPD.

Asthma is the most common noncommunicable disease in children, and among the most common in adults. The great majority of people with asthma live in low and middle income countries (LMICs), which have disproportionately high asthma-related morbidity and mortality. Essential inhaled medications, particularly those containing inhaled corticosteroids (ICS), are often unavailable or unaffordable, and this explains much of the global burden of preventable asthma morbidity and mortality. Guidelines developed for LMICs are generally based on the outdated assumption that patients with asthma symptoms <1-3 times per week do not need (or benefit from) ICS. Even when ICS are prescribed, many patients manage their asthma with oral or inhaled short-acting β2-agonists (SABA) alone, owing to issues of availability and affordability. A single ICS-formoterol inhaler-based approach to asthma management for all severities of asthma, from mild to severe, starting at diagnosis, might overcome SABA overuse/over-reliance and reduce the burden of symptoms and severe exacerbations. However, ICS-formoterol inhalers are currently very poorly available or unaffordable in LMICs. There is a pressing need for pragmatic clinical trial evidence of the feasibility and cost-effectiveness of this and other strategies to improve asthma care in these countries. The global health inequality in asthma care that deprives so many children, adolescents and adults of healthy lives and puts them at increased risk of death, despite the availability of highly effective therapeutic approaches, is unacceptable. A World Health Assembly Resolution on universal access to affordable and effective asthma care is needed to focus attention and investment on addressing this need.

Asthma is the most common non-communicable disease in children and remains one of the most common throughout the life course. The great majority of the burden of this disease is seen in low-income and middle-income countries (LMICs), which have disproportionately high asthma-related mortality relative to asthma prevalence. This is particularly true for many countries in sub-Saharan Africa. Although inhaled asthma treatments (particularly those containing inhaled corticosteroids) markedly reduce asthma morbidity and mortality, a substantial proportion of the children, adolescents, and adults with asthma in LMICs do not get to benefit from these, due to poor availability and affordability. In this review, we consider the reality faced by clinicians managing asthma in the primary and secondary care in sub-Saharan Africa and suggest how we might go about making diagnosis and treatment decisions in a range of resource-constrained scenarios. We also provide recommendations for research and policy, to help bridge the gap between current practice in sub-Saharan Africa and Global Initiative for Asthma (GINA) recommended diagnostic processes and treatment for children, adolescents, and adults with asthma.