Editors

PaulaKauppi

Long-Term Management of Asthma

Essentials

Teach the patient self-management in the follow-up and treatment Self-Management Education and Regular Practitioner Review for Adults with Asthma.
The patient's own primary care physician checks the adequacy of the treatment regularly.
The treatment aims at
- minimal symptoms
- normal functional ability
- minimal need for an on-demand bronchodilator drug
- no adverse effects of drugs
- normal or the patient's best possible pulmonary function evaluated with spirometry and PEF monitoring
- prevention of exacerbations.

Principles

Inhaled glucocorticoids treat and suppress the asthmatic airway inflammation. They are an essential part of the treatment.
All patients with asthma should also have a bronchodilator drug to be used as needed.
Teaching and follow-up of the inhalation technique of drugs is important.
The treatment should be tailored for each patient according to the severity of the disease and modified flexibly step-by-step. Self-management of drug dosing is encouraged (written instructions!).
- Provide advice on local information sources.
As necessary, inhaled glucocorticoid is combined with a long-acting beta2 agonist, long-acting anticholinergic or leukotriene receptor antagonist.
Short courses of oral glucocorticoids are occasionally needed.
- In association with a viral infection, a symptom-relieving drug (usually a short-acting beta2 agonist) is used regularly. If this is not sufficient, an oral glucocorticoid course is started. A combination of budesonide and formoterol may also be used as symptomatic therapy. If the patient uses anti-inflammatory medication only periodically (e.g. during the pollen season), the anti-inflammatory medication should be, however, used regularly also in the event of a viral infection.
High allergen concentrations may increase symptoms in a patient with allergic asthma. For example, it is not recommended for a person who has asthma and is allergic to cats to have a cat as a home pet.
High concentrations of airway irritants (dusts, fumes, chemicals) usually increase the occurrence of asthmatic symptoms.
It should be noted that people who are hypersensitive to NSAIDs cannot use aspirin or other NSAIDs (including metamizole). Approximately 10-20% of patients with asthma are hypersensitive to these drugs.
Non-selective beta-blockers often exacerbate the symptoms of asthma.
Smoking cessation is actively supported.
Allergen immunotherapy Allergen Immunotherapy may help some patients Allergen Immunotherapy for Asthma.

Implementation Intermittent Versus Daily Inhaled Corticosteroids for Persistent Asthma, Intermittent Inhaled Corticosteroid Versus Placebo for Persistent Asthma

The patient has asthma symptoms only occasionally (less frequently than once a week and nightly symptoms not more frequently than twice a month) and the pulmonary function tests are normal:
- allergy proofing of the environment and cessation of smoking Smoking Cessation
  - Reducing mite allergen levels in the environment is difficult, and there is no evidence of benefit House Dust Control Measures for Asthma.
- inhaled short-acting bronchodilator drug as needed Regular Vs. as-Needed Inhaled Short Acting Beta2-Agonist Use in Asthma (salbutamol or terbutalin or a combination preparation of budesonide and formoterol or a combination preparation of fenoterol and ipratropium bromide).
If the symptoms are more frequent and inhaled bronchodilator drugs are needed more often than once a week or if sleep is disturbed by asthma, adding regular anti-inflammatory medication is indicated.
- Inhaled glucocorticoid Inhaled Corticosteroids in the Long-Term Management of Asthma, depending on the product 100-400 µg twice (beclomethasone Beclomethasone for Chronic Asthma, budesonide Budesonide for Chronic Asthma, fluticasone propionate Inhaled Fluticasone Propionate for Asthma) or once (fluticasone furoate [only in combination preparations], ciclesonide Ciclesonide for Chronic Asthma, mometasone Mometasone for Chronic Asthma) daily Initial Starting Dose of Inhaled Corticosteroids for Asthma, Inhaled Vs Oral Steroids for Adults with Bronchial Asthma
  - Inhalation powders are usually the primary choice, easy to use and well tolerated. However, patients with weakened respiratory muscles or severely lowered vital capacity should preferably take their drugs as dose aerosols using a spacer.
  - Pulmonary concentration of drugs in aerosol form are usually better if they are taken with an inhalation spacer.
  - For clinically comparable doses of inhaled glucocorticoids, see table T1.
- A leukotriene antagonist Anti-Leukotrienes for Asthma (e.g. montelukast 10 mg for the night) may be used as an alternative. Leukotriene antagonists are particularly apt for patients who are not able to use inhaled drugs. They are well tolerated, but the effect in usual licensed doses is inferior to inhaled glucocorticoids Anti-Leukotrienes Versus Inhaled Corticosteroids in the Treatment of Asthma.
If the symptoms continue daily, if the need for an on-demand bronchodilator drug is frequent, and obstruction is present according to PEF monitoring:
- Check the inhalation techniques, recognize any factors that might worsen the asthma and verify the patient's compliance.
- To be used in addition to the inhaled glucocorticoid, add
  - a long-acting bronchodilator drug Long-Acting Beta2-Agonists in Addition to Inhaled Corticosteroids in Chronic Asthma Combination of Inhaled Long-Acting Beta-2 Agonists and Inhaled Steroids Versus Higher Dose of Inhaled Steroids in Persistent Asthma, Long-Acting Beta2-Agonists Versus Anti-Leukotrienes as Add-on Therapy to Inhaled Corticosteroids for Chronic Asthma, Safety of Regular Formoterol or Salmeterol in Adults with Asthma (salmeterol 50 µg twice daily, formoterol 6-24 µg twice daily); combined preparations containing both an inhaled glucocorticoid and a long-acting bronchodilator drug may be used instead. Single Inhaler Combination of Formoterol and Budesonide Versus Inhaled Steroid Maintenance for Chronic Asthma
  - a leukotriene antagonist Long-Acting Beta2-Agonists Versus Anti-Leukotrienes as Add-on Therapy to Inhaled Corticosteroids for Chronic Asthma
  - tiotropium bromide.
If the symptoms are not controlled adequately with a combination of a daily dose of inhaled glucocorticoid corresponding to 800 µg of budesonide (table T1) and a long-acting bronchodilator drug, added with a short-acting inhaled bronchodilator drug when needed, add one or more of the following:
- inhaled steroid at the maximum daily dose (depends on the preparation)
- leukotriene antagonist Addition of Anti-Leukotriene Agents to Inhaled Corticosteroids for Chronic Asthma (montelukast or zafirlukast)
- tiotropium bromide once daily Tiotropium Added to Long-Acting Beta-Agonist and Inhaled Corticosteroid (Laba+ics) for Adults with Asthma
- change inhaled maintenance medication for a triple preparation (inhaled glucocorticoid, long-acting beta-2 agonist and anticholinergic)
- In some cases, the following add-on drugs may be tried:
  - bronchodilator drug administered with a nebulizer
  - omalizumab Omalizumab for Asthma (anti-IgE; for allergic asthma)
  - mepolizumab, reslizumab, benralizumab (anti-IL5 and anti-IL5R; for eosinophilic asthma) or dupilumab (anti-IL4R; for eosinophilic asthma), tezepelumab (anti-TSLP)
  - regular use of a low-dose glucocorticoid in tablet form
  - azithromycin 3 times a week.
- Initiation of biological drug treatments has been concentrated to specialized care. Thermoplasty may also be considered if the patient's asthma cannot be controlled with drug therapy Bronchial Thermoplasty for Moderate or Severe Persistent Asthma in Adults.
During exacerbation, an oral glucocorticoid course is used (more details below).

Clinically comparable doses of inhaled glucocorticoids

Drug	Form*	Daily dose µg
Drug	Form*	Low	Medium	High
Beclomethasone	Powder	200-500	500-1 000	> 1 000
	HFA** solution	100-200	200-400	> 400
Budesonide	Powder	200-400	400-800	> 800
Budesonide	As part of a combination preparation	160-320	320-640	> 640
Fluticasone propionate	Powder HFA suspension	100-250	250-500	> 500
Fluticasone furoate (only in combined preparation)	Powder	-	92	≥ 184
Mometasone***	Powder	200	200-400	> 400
Ciclesonide***	HFA solution	80-160	160-320	> 320

Source: Global strategy for asthma management and prevention. Global Initiative for Asthma (GINA) 2019 http://www.ginasthma.org/ (the doses have been adjusted to the pharmaceutical preparations on the market in Finland) and Chung KF, Wenzel SE, Brozek JL ym. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur Respir J 2014;43(2):343-73. [PubMed]. The doses have been estimated according to clinical comparability. They are only indicative and may vary from patient to patient. Most of the clinical benefit of the medication is usually seen at low doses already, and evidence on dose-response relationships is limited. The risk of adverse effects is usually increased with high doses in long-term use.
* Nebulizer suspensions are not included in the table.
** HFA = hydrorofluoroalkane propellant
*** Mometasone and ciclesonide can be administered once daily.

Tapering down of medication Initial Starting Dose of Inhaled Corticosteroids for Asthma

With regard to systemic adverse effects, the low-medium doses of inhaled glucocorticoids as presented in table T1 are considered safe in maintenance therapy in adults.
As the symptoms alleviate, the medication can be tapered down gradually.
If the symptoms are minimal, if the need for inhaled bronchodilating medication is small, if the PEF values are normal, and if there is no diurnal variation, the dose of anti-inflammatory medication can be halved about 6 months after the disease has stabilized. Symptoms, periods of exacerbation and PEF values should be monitored.
In chronic asthma it is often not possible to stop all anti-inflammatory medication and this need not even be the aim, but pauses in medication may be tried every now and then.

Other aspects to be noted The Effect of Treatment for Gastro-Oesophageal Reflux on Asthma

Antimicrobial drugs are only prescribed if clear signs of bacterial infection are present.
Cough medicines have no place in the treatment of asthma.
Consider the need for pneumococcal, COVID-19 and influenza vaccination. Influenza Vaccination in Asthma: Efficacy and Side Effects
Note possible allergic or non-allergic rhinosinusitis or gastro-oesophageal reflux disease. Provide actively guidance on weight management if the patient is overweight, and giving up smoking if the patient smokes. It is not recommended for people who are allergic to animal dust to keep a domestic animal that increases allergy symptoms.

Course of oral glucocorticoids

Indications

Increasing symptoms
The effect duration of inhaled bronchodilating medication is shortening.
If PEF values are used in the assessment of a period of exacerbation, they are usually less than 80-70% of the patient's best values.
Sleep is disturbed by asthma.
Morning symptoms persist until noon.
Maximal medication without oral glucocorticoids shows no sufficient effect.
An acute exacerbation for which the patient has received nebulised bronchodilating medication in an emergency setting Corticosteroids for Preventing Relapse Following Acute Exacerbations of Asthma.

Dosage

Prednisolon is given (30-)40 mg daily usually for 5-7 days.
If the course of an oral glucocorticoid has lasted for 1 to 2 weeks it can be stopped at once without tapering the dose gradually.

Guided self-management Breathing Exercises for Adults with Asthma, Physical Training for Asthma, Self-Management of Asthma by Adjustment of Anti-Inflammatory Therapy, Increased Versus Stable Doses of Inhaled Corticosteroids for Exacerbations of Chronic Asthma, Caffeine for Asthma, Ionisers for Chronic Asthma, Beta2-Agonists for Exercise-Induced Asthma

The patient should have good knowledge of self-management.
The components of successful self-management are
- acceptance and understanding of asthma and its treatment
- effective and compliant use of drugs
- an own PEF meter at home and follow-up of results as necessary (provide the patient with instructions and a tracking chart)
- written instructions for different problems.
As a part of guided self-management the patient may receive individually tailored medication instructions in writing and, as necessary, PEF alarm thresholds.
- If there is an increase in symptoms, the patient takes a short-acting bronchodilator (or budesonide-formoterol) regularly 1-6 times a day in addition to the maintenance medication.
- If symptoms persist or worsen, self-management instructions may include a prednisolone course (e.g. 30-40 mg/day) for 5-7 days.
- The PEF thresholds to consider in association with a period of exacerbation are the following: if the morning PEF values are repeatedly less than 80-70% of the optimal value, the patient starts a course of oral prednisolone 30-40 mg daily for 5-7 days.
- If symptoms persist or worsen despite the prednisolone treatment or if the PEF value is less than 50% of the optimal, the patient should seek emergency help or contact the treating unit in addition to starting the oral prednisolone course.
During a respiratory tract infection, it is recommended to take short-acting bronchodilator 3-4 times daily on a regular basis or to increase the dose of budesonide-formoterol medication and follow other individual medication instructions.
Increasing the dose of anti-inflammatory medication may be indicated, for example, during pollen season or respiratory infection.

Referral

Specialist consultation may be needed in the situations listed below.
- Diagnostic problems
- Recurrent exacerbations
- Assessment of working ability
- Suspected cases of occupational asthma
- Severe exacerbation
- Symptoms in spite of a large dose of inhaled glucocorticoids
- Nebuliser for home use is considered.
- Biological drug therapy, thermoplasty or other special treatment is considered.
- Pregnant women with increased symptoms
- Assessment for hyposensitization therapy
- Asthma interferes with the patient's way of living (e.g. sports activities).

Follow-up Interventions Based on Sputum Eosinophils for Asthma

Asthma is mainly treated and followed up by a general practitioner.
A patient on medication should meet his/her own doctor regularly.
In mild cases one assessment of the situation yearly, either with a specialized asthma nurse Nurse Versus Physician-Led Care for the Management of Asthma or with a doctor depending on the local arrangement and remotely if deemed appropriate, is sufficient but with worsening severity of asthma more frequent follow-up visits are needed.
In addition to symptom history and lung auscultation, a one-week recording of PEF values at home can be considered for follow-up.
Spirometry Pulmonary Function Tests in order to assess the adequacy of asthma treatment is recommended for all patients every 3 to 5 years and more frequently for those who have problems in the management of their asthma.
In some patients the determination of exhaled nitric oxide (FeNO) may be useful for the adjustment of the dose of inhaled glucocorticoid in order to prevent exacerbations Exhaled Nitric Oxide Levels to Guide Treatment for Adults with Asthma; at the same time the average glucocorticoid dose may be slightly reduced.

References

Global strategy for asthma management and prevention. Global Initiative for Asthma (GINA) 2022. http://ginasthma.org/gina-reports/
[Asthma]. A Current Care Guideline. Working group appointed by the Finnish Medical Society Duodecim, Finnish Respiratory Society, Finnish Paediatric Society and Finnish Society of Clinical Physiology. Helsinki: Finnish Medical Society Duodecim 2022 (accessed 10 Jan 2023). Available in Finnish at:

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