The Global Initiative for Asthma (GINA) 2024 strategy report provides evidence-based recommendations for managing asthma. This article emphasises treatment customisation to regional resources and enhancing patient outcomes. 

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Asthma affects about 300 million people globally and is a serious global health concern that takes 1,000 lives per day. Most of these deaths occur in low- and middle-income countries and are mostly preventable. Asthma makes it difficult for people to work, school, and support a family, especially among younger people.

Asthma is becoming more prevalent and more expensive to treat for individuals, communities, and healthcare systems in many economically developing countries.

Every year, GINA publishes a strategy report with recommendations and information regarding asthma based on the most recent research. Most people on the planet live in areas with poor access to healthcare and little financial means.

GINA is aware that the recommendations made in this study must be adjusted to account for local traditions and the availability of healthcare.

To improve asthma treatment and patient outcomes, evidence-based recommendations must be provided, adopted locally and nationally, and integrated into clinical practice and health systems. Here are some freshly revealed GINA 2024 snippets.

Part 1 deals with general asthma management in adults. The second part deals with the management of acute exacerbation.

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Addressing worsening symptoms in primary care

1. The three primary therapies are controlled flow oxygen supplementation, early systemic corticosteroid introduction, and repeated administration of rapid-acting inhaled bronchodilators.
2. The objectives are to treat the underlying inflammatory pathophysiology, avoid recurrence, and quickly alleviate airway restriction and hypoxemia. Adherence to infection control protocols is crucial.

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Short-acting beta2 agonist inhalation therapy

For the treatment of acute asthma, inhaled salbutamol (albuterol) is now the standard bronchodilator.

1. Repeatedly administering inhaled SABA (up to 4–10 puffs every 20 minutes for the first hour) is a practical and efficient technique to quickly reverse airflow restriction during mild to severe exacerbations.
2. The amount of SABA needed after the first hour varies, ranging from 4–10 puffs every 3.4–5 hours to 6–10 puffs every 1.2–3 hours, or more often. If there is a satisfactory response to the first dose (e.g., PEF >60–80% of anticipated or personal best for 3–4 hours), then no more SABA is required.
3. Evidence A shows that administering SABA via a pMDI and spacer or a DPI improves lung function in a manner comparable to that of using a nebuliser; however, these trials did not involve patients who were suffering from acutely severe asthma.
4. If the patient can utilise the device, pMDI with a spacer is the most economical delivery method. Some spacers need to be pre-washed with detergent before use due to static charge. Observe the manufacturer's instructions.

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Management of acute asthma exacerbations with ICS-formoterol combination

Because it lowers the risk of severe exacerbations and exposure to OCS when compared to using a SABA reliever, combination ICS-formoterol (budesonide-formoterol or beclometasone-formoterol) is now widely used as an anti-inflammatory reliever as part of routine asthma care in adults and adolescents.

1. Based on data from major trials of its effectiveness and safety up to this level of usage, a maximum of 12 inhalations of budesonide-formoterol 200/6 mcg (160/4.5 mcg delivered dosage) may be used in a single day if necessary (total of as-needed and maintenance doses, if utilised).224,226 In light of this substantial evidence, GINA recommends that beclometasone-formoterol be used at the same maximum daily total.
2. The effects of two doses of budesonide-formoterol 400/12 mcg (delivered dose 320/9 mcg) versus eight doses of salbutamol (albuterol) 100 mcg (delivered dose 90 mcg) were compared in emergency departments among adult and adolescent patients with an average FEV 1 42–45% predicted. These doses were repeated after five minutes, and all patients received OCS.
3. Over three hours, lung function was comparable, but the SABA group's pulse rate was greater. For the treatment of acute asthma, formoterol's effectiveness and safety were shown to be comparable to salbutamol's (albuterol) in a meta-analysis of previous RCTs.733
4. Although formoterol is no longer used for this purpose, there is no proof that budesonide and formoterol would work less well together to treat asthma attacks. Further research is required. There are no published studies on the use of ICS-SABA combination therapy in emergency rooms.

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The use of controlled oxygen therapy

If pulse oximetry is available, oxygen treatment should be titrated against it to maintain oxygen saturation at 93-55% (94-98% for children aged 6-11); however, it should be noted that individuals with dark skin tones may have an overestimation of their oxygen saturation.

Titrated or regulated oxygen treatment is linked to improved results and a decreased death rate in hospitalised asthma patients when compared to high-concentration (100%) oxygen therapy.

If oximetry is not accessible, oxygen should still be given; however, because of the possibility of hypercapnia and respiratory failure, the patient should be watched closely for signs of worsening, somnolence, or tiredness. Adults should not have their oxygen saturation exceed 96% if they are given more oxygen.

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Systemic corticosteroids

1. Patients who are in danger of worsening or who have already increased their intake of ICS (Inhaled Corticosteroids)-containing drugs for relief and maintenance should get OCS (Oral Corticosteroids) as soon as possible.
2. Prednisolone is prescribed at a dosage of 1 mg/kg/day or equivalent for adults, with a daily maximum of 50 mg, and 1-2 mg/kg/day for children aged 6 to 11 years, with a daily maximum of 40 mg.
3. OCS should typically be administered for 5-7 days for adults and 3-5 days for kids. Patients should be informed of the typical short-term adverse effects, including mood swings, increased hunger, reflux, and disturbed sleep.
4. Following a brief course of OCS in adults, there is also an elevated risk of sepsis and thrombosis. While OCS may save an adult's life in cases of acute, severe asthma, using them for four to five-lifetime courses is linked to a dose-dependent increase in the risk of long-term side effects such as cataracts, diabetes, heart failure, osteoporosis, and fractures.
5. This highlights how crucial it is to maximise asthma treatment after any significant exacerbation to lower the likelihood of further exacerbations.

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Maintenance ICS-containing medication

1. Patients who have previously been given maintenance medicine containing ICSs should be advised to boost their dosage for the next two to four weeks.
2. Individuals who are not presently using controller medication have to start on ICS-containing therapy, since SABA-only asthma treatment is no longer advised.
3. An exacerbation that necessitates medical attention suggests that the patient is more vulnerable to exacerbations in the future.

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Antibiotics (not recommended)

When treating acute asthma exacerbations, antibiotics should not be used routinely unless there is clear evidence of a lung infection, such as fever and purulent sputum or radiographic evidence of pneumonia.

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Therapy administered in emergency rooms and other acute care settings

Generally, the subsequent treatments are administered simultaneously to facilitate a swift recovery.

Oxygen

1. To get an arterial oxygen saturation of 93-55% (or 94-58% in children aged 6-11), oxygen has to be delivered by nasal cannulae or masks.
2. Take note of the possibility that individuals with dark skin tones may overestimate their saturation. Controlled low-flow oxygen treatment, which uses pulse oximetry to maintain saturation at 93%–95%, is linked to better physiological results in severe exacerbations than high-concentration (100%) oxygen therapy.
3. If pulse oximetry is not available, oxygen treatment should not be stopped. Use oximetry to guide the patient's requirement for further oxygen treatment after they have stabilised.

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Short-acting beta2 agonists inhaled

1. For the treatment of acute asthma, inhaled salbutamol (albuterol) is now the standard bronchodilator. The most economical and successful delivery method is pMDI with a spacer.
2. In cases of severe and almost deadly asthma, the evidence supporting pMDI and spacer is weaker.
3. The outcomes of systematic studies that primarily employed nebulised SABA in acute asthma, and compared intermittent vs continuous SABA, are inconsistent.
4. Nebuliser use can disperse aerosols and may facilitate the transmission of viral respiratory illnesses.
5. The majority of individuals experiencing severe asthma exacerbations do not now have evidence to justify the regular use of intravenous beta 2 agonists.

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The ICS-formoterol combination as a substitute for high-dosage SABA

Formoterol has been shown to have comparable effectiveness and safety to SABA in emergency department trials, as well as in one research including budesonide-formoterol.

Subsequent research revealed that high-dose SABA and budesonide-formoterol had comparable safety and effectiveness profiles.

Patients in this trial were given either 8 doses of salbutamol (albuterol) 100 mcg (delivered dose 90 mcg) or 2 doses of budesonide-formoterol 400/12 mcg (delivered dose 320/9 mcg), repeated once every 5 minutes.

All patients received OCS. A meta-analysis of data from previous trials comparing high-dose formoterol with high-dose salbutamol (albuterol) for the treatment of acute asthma in the emergency department (ED) setting suggests that budesonide-formoterol might also be beneficial, while additional research is required. For this reason, formoterol alone is no longer utilised.

For anaphylaxis, epinephrine is prescribed.

In addition to conventional treatment, intramuscular epinephrine (adrenaline) is recommended for acute asthma linked to anaphylaxis and oedema. It is not usually used for additional episodes of asthma aggravation.

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Systemic corticosteroids

In acute care settings, systemic corticosteroids should be used for all but the mildest exacerbations in adults, adolescents, and children aged 6 to 11 years. They expedite the resolution of exacerbations and prevent recurrence.

Systemic corticosteroids (ICS) should be given to the patient as soon as feasible after presentation; high-dose ICS have been shown in certain trials to provide comparable benefits.

Systemic corticosteroids should be used in the emergency room in the following situations:

• The patient's symptoms worsened while on OCS
•  The patient's symptoms did not improve after starting SABA therapy
• There is a history of OCS-requiring exacerbations in the patient's past

Delivery method:

1. Oral medication is just as effective as intravenous. Because it is less costly, less intrusive, and faster, the oral route is recommended. A liquid formulation is better than pills for kids.
2. At least four hours are needed for OCS to result in a clinical improvement. When patients are vomiting, too dyspneic to swallow, or in need of non-invasive ventilation or intubation, intravenous corticosteroids may be given. There is insufficient evidence to support the superiority of injectable corticosteroids over oral corticosteroids.

Dosage: Adults are usually prescribed daily dosages of OCS equal to 50 mg prednisolone given as a single morning dose or 200 mg hydrocortisone given in split doses. Prednisolone dosage recommendations for children are 1-2 mg/kg up to a daily maximum of 40 mg.

Duration:

1. In adults, 5- and 7-day doses of prednisone or prednisolone have been proven to be as effective as 10- and 14-day courses, respectively, while a 3- to 5-day term is often thought to be enough for the majority of children.
2. There is no evidence to support the idea that reducing the dosage of OCS over a few weeks or in the near term is beneficial, based on trials where all patients were on maintenance ICS after discharge.
3. A few studies looked at individuals who took oral dexamethasone 12–16 mg once a day for 1-2 days; the relapse and adverse event rates were comparable to those of those who took prednisolone for 3-5 days.
4. A comprehensive analysis conducted on children revealed that there was no difference in the recurrence rate between oral dexamethasone (0.3 mg/kg or 0.6 mg/kg once daily) and oral prednisone/prednisolone (3-5 days); however, there was improved adherence and a significantly decreased risk of vomiting with dexamethasone.

Inhaled corticosteroids

1. In the ER, patients who are not taking systemic corticosteroids may avoid the requirement for hospitalisation by administering high-dose ICS within the first hour of presentation. Adult data on adding to systemic corticosteroids is inconclusive.
2. In children, giving ICS during the first few hours after arriving at the ER, with or without concurrent systemic corticosteroids, may lower the likelihood of hospitalisation and the need for systemic corticosteroids.
3. In general, add-on ICS are well tolerated; nevertheless, cost could be a big consideration, and it's still uncertain which medication to use, how much to take, and how long to take it for while treating asthma in the ER. Patients who are hospitalised due to an exacerbation of their asthma should be given or kept on ICS-containing medication.
4. As the incidence of a severe exacerbation is a risk factor for future exacerbations, patients should be given continued ICS-containing therapy upon return home. Additionally, the use of ICS-containing drugs dramatically lowers the risk of hospitalisation or death from asthma.
5. Treatment of asthma with SABA alone is no longer advised. A comprehensive study revealed no statistically significant changes in short-term outcomes (i.e., recurrence necessitating hospitalisation), symptoms, and quality of life when ICS was added to systemic corticosteroids after discharge.
6. Though the confidence intervals were large, there was some indication that, for milder exacerbations, post-discharge ICS were just as beneficial as systemic corticosteroids. More research is needed to determine the effect that cost may have on patients' decision to take high-dose ICS. Cost may be a major concern for patients.
7. The recommended course of treatment after an ED visit or hospital stay is maintenance-and-reliver therapy (MART) with ICS-formoterol.
8. When combined with as-needed SABA at a higher dosage or ICS-LABA at a lower dose, MART lowers the risk of another severe exacerbation in patients who have had at least one severe exacerbation by 23% and 32%, respectively, over the following 12 months.

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Other treatments

Ipratropium bromide

Treatment in the emergency room with both SABA and ipratropium, a short-acting anticholinergic, was linked to fewer hospitalisations and a higher improvement in PEF and FEV1 for adults and children with moderate-to-severe exacerbations than with SABA alone.

Ipratropium added to SABA did not improve outcomes for children hospitalised for acute asthma, such as shorter hospital stays, although it did lower the risk of nausea and tremors.

Theophylline and aminophylline (not advised)

Because SABA is more productive and relatively safe than intravenous aminophylline and theophylline, these medications should not be used to treat asthma exacerbations due to their low efficacy and safety profile.

When using aminophylline, nausea and vomiting are more frequent. Severe and perhaps deadly adverse effects are linked to intravenous aminophylline usage, especially in patients on sustained-release theophylline therapy.

When compared to SABA alone, add-on therapy with aminophylline did not enhance outcomes for people experiencing severe asthma exacerbations.

Magnesium

It is not advised to use intravenous magnesium sulfate for asthma exacerbations routinely; however, in certain patients, such as adults with a predicted FEV 1 of less than 25–30% at presentation, adults and children who do not respond to initial treatment and have persistent hypoxemia, and children whose predicted FEV 1 does not reach 60% after one hour of care, it can reduce hospital admissions.

In the regular treatment of asthma exacerbations in adults, adolescents, or children, randomised, controlled studies that excluded individuals with more severe asthma did not demonstrate any advantage with the addition of intravenous or nebulised magnesium when compared with placebo.

Treatment with helium-oxygen

A comprehensive evaluation of research comparing helium and oxygen to air and oxygen indicates that this intervention is not useful for normal treatment. However, individuals who do not respond to usual therapy may benefit from it; availability, cost, and technical considerations should be taken into account.

Antagonists of the leukotriene receptor (LTRAs)

The use of oral or intravenous LTRAs for acute asthma is not well-supported by research. Although several small trials have shown improvements in lung function, additional research is needed to determine the therapeutic use and safety of these medicines.

Antibiotics: not advised

Unless there is clear evidence of a lung infection (such as fever, purulent sputum, or radiographic evidence of pneumonia), there is no evidence to support the regular use of antibiotics in the treatment of acute asthma exacerbations.

Non-invasive ventilation (NIV)

1. There is little data to support the idea that NIV causes asthma. Five trials involving 206 persons with acute severe asthma treated with NIV or placebo were found via a systematic review.
2. One research revealed that the NIV group had fewer admissions, while two trials found no change in the requirement for endotracheal intubation. Both studies did not record any fatalities.
3. Considering the tiny sample sizes of the research, no suggestions are made. Should NIV be attempted, the patient has to be properly watched. It should not be attempted in agitated patients, and patients should not be sedated to receive NIV Sedatives (MUST BE AVOIDED)
4. Because anxiolytics and hypnotics have a respiratory depressive effect, sedation should be rigorously avoided during asthma flare-ups. There has been evidence of a link between the usage of these medications and preventable asthma fatalities.
5. For further detailed information, readers are requested to go through the references.

Click here to read the first part of this article- Global Asthma Management: GINA 2024 Guidelines: Part 1

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Monish Raut is a practising super specialist from New Delhi.