The Saudi Initiative for Asthma 2021 (SINA-2021) is the fifth version of asthma guidelines for the diagnosis and management of asthma for adults and children, which is developed by the SINA group, a subsidiary of the Saudi Thoracic Society. The main objective of the SINA is to have guidelines that are up to date, simple to understand, and easy to use by healthcare workers dealing with asthma patients. To facilitate achieving the goals of asthma management, the SINA panel approach is mainly based on the assessment of symptom control and risk for both adults and children. The approach to asthma management is aligned for age groups: adults, adolescents, children aged 5–12 years, and children aged less than 5 years. SINA guidelines have focused more on personalized approaches reflecting better understanding of disease heterogeneity with the integration of recommendations related to biologic agents, evidence-based updates on treatment, and the role of immunotherapy in management. Medication appendix has also been updated with the addition of recent evidence, new indications for existing medication, and new medications. The guidelines are constructed based on the available evidence, local literature, and the current situation at national and regional levels. There is also an emphasis on patient–doctor partnership in the management that also includes a self-management plan.
Keywords: Asthma, asthma control test, guidelines, Saudi Arabia
Asthma is a chronic heterogeneous disease usually characterized by chronic airflow limitation. It is defined by the history of respiratory symptoms such as wheeze, shortness of breath, chest tightness, and cough that vary over time and in intensity, together with variable expiratory airflow limitation.[1] Asthma is one of the most common chronic diseases in Saudi Arabia, with an increasing prevalence in the past decades.[2] It has a significant impact on patients, their families, and the community as a whole in terms of lost work and school days, poor quality of life, frequent emergency department (ED) visits, hospitalizations, and deaths.[3],[4],[5] As part of its long-term commitment to promote best practice in the field of respiratory diseases, the Saudi Thoracic Society (STS) launched the Saudi Initiative for Asthma (SINA) group in 2008. The SINA panel is a group of Saudi experts with well-respected academic backgrounds and experience in the field of asthma. Sections related to asthma in children represent the views of a panel from the Saudi Pediatric Pulmonology Association, another subsidiary of the STS.
The SINA panel aims to have updated guidelines, which are simple to understand and easy to use. It also aims toward enhancing the multidisciplinary care of asthma patients with special attention to nonasthma specialists, including primary care and general practice physicians and other healthcare workers.[6],[7],[8],[9] The updated 2021 version of SINA guidelines received a comprehensive update with an emphasis on personalized approaches reflecting a better understanding of disease heterogeneity with an integration of recommendations related to new medications, approved biologic agents, evidence-based updates on treatment, especially on mild asthma, and the role of immunotherapy in management. A special attention is made to managing asthma during the time of emerging acute respiratory infections, such as the recent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The SINA panel stratified the guidelines based on the following age groups: adults: age above 18 years; adolescents: age of 13–18 years; and children who were stratified into two groups: age of 5–12 years and age below 5 years.[10]
Methods
The SINA guidelines document was initially based on the Global Initiative for Asthma (GINA) strategies with reference to related major international guidelines.[10] The SINA is supplemented by the available local literature and the current setting in Saudi Arabia. Consensus among the SINA panel was followed whenever there was lack of evidence.[11] The following criteria are used to grade the evidence:
Evidence Category A: Randomized controlled trials with rich body of dataEvidence Category B: Randomized controlled trials with limited body of dataEvidence Category C: Nonrandomized trials and observational studiesEvidence Category D: SINA panel consensus judgment. This category is only used in cases where the provision of some guidance was deemed valuable, but the clinical literature addressing the subject was insufficient to justify the placement in one of the other categories.For this update, the similar approach to previous updates has been employed, whereby each section has been internally reviewed at least twice by the SINA panel members. The SINA panel conducted frequent round-table and virtual discussions. A panel of international experts reviewed the guidelines and their recommendations were thoughtfully considered.
Epidemiology
Asthma is one of the most common chronic illnesses in Saudi Arabia, and local reports suggest that the prevalence of asthma is increasing.[3],[12],[13] Inadequate knowledge, unfamiliarity with new drugs, and lack of awareness of the importance of disease control are common among primary care physicians who care for asthma patients in Saudi Arabia.[14],[15] In addition to these key factors, there are other attributes to the magnitude of disease burden such as socioeconomic status, number of siblings, knowledge of caregivers, and income.[16],[17],[18],[19] Consequently, many asthma patients are uncontrolled and continue to be under-diagnosed, under-treated, and at risk of acute attacks, resulting in missed work or school, increased use of expensive acute healthcare services, and reduced quality of life.[12],[20] This was also observed among pregnant women with asthma as one study from Saudi Arabia showed that almost half of pregnant women had the intention to stop asthma medications during pregnancy.[21]
A meta-analysis on the prevalence of asthma in different regions in Saudi Arabia showed a rise in the prevalence from 1990 to 2000, with stabilization in the prevalence of asthma since 2000.[3] The pooled weighted prevalence rate of asthma was 14.3%, lifetime wheeze was 16.5%, and rhinitis was 21.4%. The prevalence of asthma varied in different regions without any disparity in prevalence in the rural and urban areas of Saudi Arabia.[3] The overall prevalence of asthma in children from Saudi Arabia has been reported to range from 8% to 25%, based on studies conducted over the past three decades. The increasing prevalence of asthma in the past three decades may be attributed to rapid lifestyle changes related to the modernization of Saudi society, changes in dietary habits, and exposure to environmental factors, such as indoor allergens, dust, sandstorms, and tobacco. In addition, this high prevalence of asthma could be attributed to an increase in asthma awareness in the general population and among healthcare workers, allowing more individuals to be diagnosed. Other explanations have attributed the increased prevalence to the hygiene hypothesis, which proposes that there is a lack of sufficient microbial exposure early in life due to pharmacological manipulations and vaccines.[22],[23]
Most of the studies investigating the prevalence of asthma in various countries have focused on children aged below 15 years or adults aged above 18 years. A study conducted by the STS investigated the prevalence of asthma and its associated symptoms in 16–18-year-old adolescents attending high schools in Riyadh.[24] This study utilized the International Study of Asthma and Allergies in Children (ISAAC) questionnaire tool. Out of 3073 students, the prevalence of lifetime wheeze, wheeze during the past 12 months, and physician-diagnosed asthma was 25.3%, 18.5%, and 19.6%, respectively. The prevalence of exercise-induced wheezing and night coughing in the previous 12 months was 20.2% and 25.7%, respectively. The prevalence of rhinitis symptoms in students with lifetime wheeze, physician-diagnosed asthma, and exercise-induced wheeze was 61.1%, 59.9%, and 57.4%, respectively. Rhinitis symptoms were significantly associated with lifetime wheeze, physician-diagnosed asthma, and exercise-induced wheeze. By utilizing the ISAAC questionnaire method, another study conducted among 5188 primary schoolchildren in Madinah showed that the prevalence of asthma was 23.6%, while 41.7% had symptoms suggestive of at least one allergic disorder.[25] A national Saudi household survey conducted in 2013 estimated the self-reported clinical diagnosis of asthma to be 4.05%.[26] Another survey using the European Community Respiratory Health Survey questionnaire, conducted in Riyadh among a total of 2405 Saudi nationals aged 20–44 years, showed that the prevalence of wheezing in the last 12 months was 18.2% and physician-diagnosed asthma reported was 11.3%. There were no significant differences between asthmatic and nonasthmatic patients, with respect to living area, level of education, and vaping history.[2]
Among a group of university students in Najran, a report revealed that the overall prevalence of physician-diagnosed allergic diseases was 27% for asthma, 13.1% for atopic dermatitis, and 5% for allergic rhinitis.[27] The prevalence of physician-diagnosed asthma among school students in Jazan, Najran, Taif, and Madinah was 10%, 27%, 13%, and 23%, respectively.[28] A cross-sectional study conducted in adult patients with asthma who attended primary care clinics at three major hospitals in Riyadh reported that 58.9% of men and 77.0% of women had uncontrolled asthma. Factors associated with uncontrolled asthma were stress, smoking, obesity, and low socioeconomic status.[29] In the Epidemiological Study on the Management of Asthma in Asthmatic Middle East Adult population, 1009 patients from Saudi Arabia were analyzed and found that 30.1% have controlled asthma. Controlled asthma was more prevalent among male patients and those with high educational level, while age, body mass index, and adherence to treatment were found to have no effect on asthma control.[30]
Data regarding the relationship between asthma and SARS-CoV-2 are limited, and most of the current knowledge was derived from studies addressing the outcomes of multiple medical conditions, including asthma on patients with COVID-19. The most frequent trigger factor of asthma exacerbation is airway infections, particularly viral infection. However, interestingly, SARS-CoV-2 infection does not increase the risk of asthma exacerbations or mortality. Several studies including several thousand patients from different countries found that the comorbidity rates of COVID-19 with asthma were significantly low. In a review of 1265 consecutive patients, the prevalence of asthma was found to be 12.6%. When compared with nonasthmatics, COVID-19 did not lead to a significant impact on length of stay, hospital readmission, intubation, tracheostomy tube placement, or mortality.[31] Older adults with underlying chronic medical conditions such as hypertension, diabetes, cardiovascular diseases, obesity, chronic obstructive pulmonary disease (COPD), but not asthma are at a higher risk of severe COVID-19 and death.[32],[33],[34],[35] In spite of this, the SINA panel emphasizes that physicians should not underestimate COVID-19 in asthma patients. Asthma medications should continue the same and the physicians should follow the usual step approach management of asthma. It is worth to notice that the knowledge regarding COVID-19 is rapidly growing, and by the time of publishing these guidelines, maybe new data will be published in regard to the interaction between asthma and SARS-CoV-2, we highly encourage the reader to keep updated to the most recent data.
Asthma is a chronic inflammatory airway disease that results in narrow airway lumen. The airway narrowing is caused by increased mucus secretion as well as bronchial wall thickening due to edema, smooth muscle hypertrophy, and subepithelial fibrosis. The pathophysiological mechanisms that underlie these changes are diverse and heterogeneous [Box 2.1]. They are driven by a variety of cell types including immune cells; mainly T-helper cells (Th2, Th17, Th1), B-cells, mast cells, eosinophils, dendritic cells, and neutrophils; as well as structural bronchial cells such as epithelial cells, myofibroblasts, and smooth muscle cells.[36] These mechanisms can be broadly classified into four categories (endotypes). Other classifications exist, but this classification is more pertinent to severe asthma and therefore has special implications on biological therapy.
Type 2-high (eosinophilic) asthma
This is the most common type and includes 40%–70% of asthma patients. It is defined by sputum eosinophilia of ≥2% of leukocytes in a sample. Patients frequently have blood eosinophilia of ≥150/μL and FeNO ≥20 ppb. This eosinophils' cutoff is way below the lower normal peripheral eosinophil count. This is because patients with severe asthma are already on high-dose inhaled corticosteroids (ICSs) or maintenance systemic oral corticosteroid (OCS). Eosinophils secrete mediators such as major basic protein and eosinophil cationic protein that can cause bronchial epithelial damage and subepithelial fibrosis. Those patients usually respond well to ICSs, especially if they have mild or moderate disease. It is further subdivided into two types:
Early-onset allergic eosinophilic airway inflammation (extrinsic asthma) type usually starts in childhood and can be triggered by allergen exposure. Allergens are taken up by dendritic cells and presented to naïve T-cells that develop into Th2 cells characterized by the secretion of type 2 cytokines: interleukin (IL)-4, 5, and 13. IL-4 and 13 are necessary for specific B-cell activation and switching into immunoglobulin (Ig) E-producing cells. IgE binds to its high affinity receptor on mast cells. Subsequent cross-linking of IgE molecules by the allergen will lead to mast cell degranulation and release of mediators, such as histamine and tryptase as well as type 2 cytokines. In addition, IL-13 causes smooth muscle and goblet cell hyperplasia. On the other hand, IL-5 is essential for eosinophil maturation and survival and contributes with certain other chemokines to their recruitment to the bronchial airways.[37],[38] Symptoms could also be triggered by similar triggers of the nonallergic type (see below)Late-onset nonallergic eosinophilic airway inflammation (intrinsic asthma) type usually starts during adulthood. Patients typically have no allergies but usually more severe airway limitation and airway hyperresponsiveness (AHR). It is triggered by microbes (bacteria and viruses), pollutants, and irritants. Bronchial epithelial cells will subsequently release IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) that will stimulate innate lymphoid cells type 2 to release IL-5 and IL-13.[39]Type 2-low (noneosinophilic) asthma
This can further be subdivided into two types:
Neutrophilic inflammation is variably defined as neutrophils of ≥40%–60% of leukocytes in an induced sputum sample. It is less clearly characterized and involves release of Th1- and Th17-related cytokines and IL-8, GM-CSF that attracts neutrophils to the airways. It is triggered by infections, irritants, and tobacco smoke and may be a manifestation of the use of steroids in patients with eosinophilic inflammation. Those patients are mostly adults and do not respond to ICSs as well[40]Paucigranulocytic inflammation is not as much inflammation. The airway limitation is supposedly driven by other mechanisms. It is the least common and patients usually have milder disease.[41]Mixed type 2-high and type 2-low (granulocytic) asthma
This type has features of both eosinophilic and neutrophilic inflammation including their cytokine profile. It is less common than the two previous main types and tends to be more severe and more difficult to treat.[42]
Airway hyperresponsiveness
AHR is a major feature of all asthma endotypes. Its mechanisms and mediators are poorly understood. It worsens during and immediately after asthma attacks. It is usually worse in patients with severe asthma. However, it does not correlate well with markers of inflammation. Smooth muscle hypertrophy and neurohumoral factors may play a role in determining AHR.[43]
Airway remodeling
This is a major feature of asthma that starts early in the disease process and causes incomplete reversibility by bronchodilators. It is characterized by bronchial epithelial damage, thickening of the basement membrane, and muscle hypertrophy.[44],[45] It is influenced by the ongoing airway inflammation and recurrent bronchoconstriction.[46]
Pathophysiology of acute asthma
The pathophysiology of acute asthma is less clear due to limited information. This is because of the difficulty in studying disease pathology and obtaining samples during exacerbations. The pathological manifestations generally depend on the trigger. At least 80% of cases of moderate-to-severe acute asthma are triggered by viruses, most commonly rhinovirus but also respiratory syncytial and influenza viruses.[47] Viral infections can cause significant epithelial damage and symptoms tend to be more severe and last longer. On the other hand, allergen- or irritant-triggered attacks tend to be milder and resolve more quickly. Recurrent attacks may lead to progressive decline in lung function and increasing baseline asthma severity.[48],[49],[50]
The diagnosis of asthma is based on clinical assessment by a detailed history and physical examination supported by spirometry with reversibility testing.
History
The symptoms of asthma are wheezing, cough, shortness of breath, and chest tightness, but they are not specific for asthma and can be seen with other pulmonary diseases. However, the combination of these symptoms increases the probability of asthma. The pattern of symptoms is usually variable over time, and the patient may be entirely asymptomatic between attacks.[51],[52] Symptoms are usually worse at night, particularly in children, and can be provoked by exercise or other triggering factors such as viral infections and/or smoke. Asthma diagnosis can be supported by taking detailed history including patient's occupation, family history of asthma, other allergic disorders, and smoking and vaping. [Box 3.1] lists the relevant questions that are commonly considered when taking a history where the diagnosis of asthma is under consideration. Asthma control may be worsened by coexisting symptomatic gastroesophageal reflux disease (GERD), rhinosinusitis, obesity, sleep disorders, or the use of some medications such as beta-blockers and nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin (ASA).[53],[54] Asthma and rhinosinusitis commonly coexist.[55],[56]
Physical examination
The physical examination of the chest may be normal in stable and controlled asthma, but the presence of bilateral expiratory widespread, high-pitched, variable musical wheezing is a characteristic feature of asthma. This may be accompanied by shortness of breath or diminished oxygen saturation. Examination of the upper airways is important to look for evidence of allergic rhinitis, such as nasal mucosal swelling, nasal polyps, and postnasal dripping. Other allergic manifestations, such as atopic dermatitis, also support the diagnosis of allergic asthma.[51],[57] The presence of a localized wheeze, crackles, stridor, clubbing, or heart murmurs should suggest alternative diagnoses.[58],[59] Therefore, a careful consideration of any alternative diagnoses before commencing asthma treatment by a physician should be made.
Investigations
Spirometry is necessary to confirm airflow obstruction and demonstrates a significant reversibility by performing a spirometry. The degree of significant reversibility is defined as an improvement in FEV1 ≥12% and ≥200 mL from the prebronchodilator value.[60] It may also help to identify other alternative diagnoses such as upper airway obstruction. However, normal spirometry or failure to show reversibility does not rule out the diagnosis of asthma as it can be normal with the patient still being symptomatic.[61],[62] Serial peak expiratory flow (PEF) rate measurements may be helpful in the diagnosis of asthma by showing the characteristic increased variability and for follow-up after starting treatment. Bronchoprovocation testing is another tool to rule out asthma with atypical presentation and normal spirometry, but it is not routinely required. A diagnostic therapeutic trial with an ICS and a bronchodilator combination may be useful in confirming a diagnosis when it shows a favorable response.[62]
Chest X-ray (CXR) is not routinely recommended unless the diagnosis is in doubt, when symptoms are not typical or suggest alternative diagnoses. Peripheral eosinophilia and elevated IgE level are supportive of the diagnosis but are not routinely recommended unless dealing with moderate-to-severe asthma. Exhaled nitric oxide is an alternative method for detecting airway inflammation in eosinophilic asthma, but it is not widely available and can be suppressed with the use of ICSs in smokers.[63] Skin prick testing and radioallergosorbent test (RAST) may be helpful in identifying allergens to which the patient has been sensitized and in developing a strategy for avoiding allergen exposure.[64]
Principles of asthma assessment
The principles of optimal asthma management is recommended to initially consist of an assessment of asthma control.[65] Before commencing a patient on treatment, the SINA panel recommends ensuring the following:
Assessment of asthma controlAssessment of risk factors for poor asthma control and fixed airway obstructionPerformance of pulmonary function testing with spirometry and/or PEF to assess for airflow limitations and postbronchodilator reversibilityDocumentation of current treatment and any issues related to adherence, inhaler technique, or side effectsUtilization of a written asthma action planAssessment of comorbidities such as rhinosinusitis, GERD, obesity, obstructive sleep apnea, anxiety, and exercise-induced laryngeal obstruction[66]Close monitoring for patients with severe asthma and history of asthma attacks.Assessment of asthma symptoms control
In adults and adolescents, asthma control is based on assessing asthma symptoms, use of reliever medications, and impact on daily activities. Asthma control reflects the adequacy of management by describing the clinical status of a patient as controlled, partly controlled, or uncontrolled over the past 4 weeks. The control status may vary markedly over time and is recommended to entail frequent assessment of current asthma status, asthma burden, and medical management.[67] Focusing on asthma control may improve patient perceptions and expectations that improve symptoms reporting and subsequently treatment decisions by clinicians.[68] Poor asthma control is associated with increased burden of the disease, asthma attacks, and mortality.[69] Therefore, symptoms control assessment should be carried out during any clinical evaluation. The SINA panel recommends the utilization of either the GINA assessment of asthma symptoms' control or the asthma control test (ACT).
Global Initiative for Asthma assessment of asthma symptoms' control
It is a short questionnaire utilized to assess asthma control over the past 4 weeks [Box 4.1].[1],[70] It consists of four items: (1) daytime symptoms more than twice a week, (2) any night waking due to asthma, (3) reliever needed for symptoms more than twice a week, and (4) any activity limitation due to asthma.[1] Control status is classified as follows:
Asthma control test
The ACT is a commonly used tool to assess asthma control which is correlated with the GINA asthma symptoms assessment.[71],[72] It is a short, validated, self-administered questionnaire to assess asthma control in the past 4 weeks [Box 4.2].[73],[74] It consists of five items including limitation of activity, shortness of breath, frequency of night symptoms, use of rescue medication, and rating of overall control of the disease over the past 4 weeks.[74] The score of ACT is the sum of the five questions where each is scored from 1 (worst) to 5 (best), leading to a maximum best score of 25. The SINA panel recommends the utilization of ACT to initiate asthma treatment in adults and adjust it at follow-up.[75],[76],[77] The clinically important a significant change in ACT score is considered to be ≥3 units.[78] The level of asthma control is categorized into:
Assessment of risk factors for future asthma attacks
The future risk of adverse outcomes should be assessed. This is achieved by assessing future risk of attacks, fixed airflow obstruction, and adverse effect of medications.[1] The SINA panel recommends the assessment of risk factors for poor asthma outcomes, especially in patients experiencing attacks by assessing risk factors for:
Independent risk factors for acute severe asthma attacks in the past 12 months or prior history of admission to an intensive care unit (ICU), especially if intubated[79],[80]Other modifiable risk factors are recommended to be addressed, such as high usage of relievers, frequent use of OCS, low forced expiratory volume in the 1st s (FEV1), pregnancy, inadequate ICS, smoking and vaping, comorbidities, major psychological disorders, reduced socioeconomic status, and presence of comorbiditiesRisk factors for fixed airway obstruction including inadequate ICS treatment, exposure to tobacco smoke or other noxious substances, low initial FEV1, or sputum/blood eosinophilia.[81]Asthma severity assessment in clinical practice
There is a trend in clinical practice to retrospectively assess asthma severity based on the step of treatment required to control symptoms and attacks.[10],[81],[82],[83] Before classifying asthma severity, it is essential to ensure that control is achieved and maintained while using the minimal level of medications over a few months.[1] Since asthma severity level could change over years or months, asthma level of severity can be classified as follows:
Mild asthma: Controlled asthma at step 1 or 2Moderate asthma: Controlled asthma at step 3Severe asthma: Asthma that requires treatment step 4 or 5.Assessment when control is not achieved
If asthma control is not achieved at any step during therapy, the SINA panel recommends assessing the following:
Appropriateness of prescribed medications and dosesPatient's adherence and correct technique in using devicesSelection of the appropriate device and appropriate spacer with pressurized metered-dose inhaler (pMDI) deviceObstacles in taking prescribed medications (e.g., cost, time, and patients' concerns on lack of perceived need)Environmental exposure to allergens at homeAssessment of comorbidities such as rhinosinusitis, GERD, obesity, obstructive sleep apnea, and anxietyFuture risk of attacks and fixed airflow obstruction.The long-term goal of asthma therapy is to achieve and maintain asthma control by utilizing pharmacological and nonpharmacological measures [Box 5.1]. The appropriate implementation of nonpharmacological measures also aims to use the least possible doses of asthma medications to minimize their side effects.
Developing a partnership with the patient
The development of a partnership between patients and healthcare professionals leads to the enhancement of knowledge, skills, and attitude toward a better understanding of asthma and its management. Based on agreed goals of management, a written self-management action plan should be offered to all patients. A wide variety of plans are available. This is expected to reflect positively on patient adherence, which is a major issue in the management. Factors leading to nonadherence may be related to poor inhaler technique, a regimen with multiple drugs or devices, concern regarding side effects from the drugs, and cost of medications.[84],[85],[86],[87] Other factors include lack of knowledge about asthma, lack of partnership in its management, inappropriate expectations, underestimation of asthma symptoms, use of unconventional therapy, and cultural issues.[30],[88]
Asthma education
The goal of asthma education is to provide patients with adequate training to enhance their knowledge and skills to be able to adjust treatment, according to guided self-management plan.[89],[90],[91],[92] To enhance the level of knowledge and skills among asthma patients, it is recommended to include knowledge about asthma and skills related to prescribed inhaler devices, as there may be misperceptions about the use of inhalers and the safety of ICSs [Box 5.2].[93],[94],[95],[96] Asthma education should be conducted by a well-trained healthcare worker, who has good communication skills and is able to create an interactive dialog in a friendly environment. With the availability of appropriate information, patients are expected to continue on the management plan and be reassured about the control of their asthma.[97] It is essential to get feedback from the patient to maintain a bidirectional rapport. Reproducible evidence has shown that a well-structured asthma education program improves the quality of life, reduces cost, and decreases the utilization of healthcare resources.[98],[99],[100] Asthma should be structured based on available resources.
Identify and reduce exposure to risk factors
Measures to prevent or reduce exposures to risk factors should be implemented wherever possible. There are different triggers leading to acute asthma attacks, which may include allergens, viral infections, pollutants, drugs, and occupational agents. These factors can be classified as indoor or outdoor allergens and occupational sensitizers.
Indoor allergens and air pollutants
There is a wide spectrum of indoor allergens that include dust mites, animals (mainly cats), cockroaches, and fungi (e.g., Alternaria and Aspergillus). Single-allergen interventions are likely to fail. However, multifaceted, tailored, and intensive interventions may help in improving asthma control. There are still several gaps in the literature in this area. It may take a few months for the allergen level to become significantly lower from the implementation of the related control measures.[101] The most important indoor air pollutant is related to tobacco exposure. Measures to avoid tobacco exposure are expected to lead to better asthma control and avoidance of long-term lung function impairment.
Outdoor allergens and dust
Outdoor allergens such as pollens and molds are impossible to avoid completely; however, exposure may be reduced by closing windows and doors and using air conditioning. It is recommended to avoid strenuous outdoor physical activities in cold weather, low humidity, or high air pollution. In a single-center study in Saudi Arabia, sandstorms were shown to worsen asthma symptoms but not hospital admission in children with asthma. It is advisable to avoid going out in the storm, especially for those with uncontrolled asthma.[102]
Occupational exposures
Whenever an occupational sensitizer is identified, it is advisable to keep the affected person away from that environment. The earlier the removal of this sensitizer takes place, the higher the chance of complete recovery from occupational asthma (See Asthma in Special Situation).
Food and drugs
Food and food additives are uncommon triggers of asthma. Avoidance is not generally recommended until it is documented by a specialist. However, certain drugs that could worsen asthma symptoms should be avoided (e.g., beta-blockers), whenever possible.
Vaccination
Annual influenza vaccination is strongly recommended for individuals with asthma, especially those with severe asthma.[103],[104],[105] It usually becomes available early on the fall season. Pneumococcal vaccination is also recommended as per the local guidelines.[106]
The SINA panel recommends asthma treatment to be based on the following phases:
Initiation of treatmentAdjustment of treatmentMaintenance of treatment.At each phase, the patient is recommended to have a clinical assessment that includes symptoms assessment by ACT, a physiological measurement with PEF or spirometry, review of current medications and patients' adherence and inhaler technique, a risk for attacks, and the response to treatment. Based on the clinical and physiological assessment, the patient is placed on the appropriate treatment step. Medication Appendix contains more information about medications used in asthma treatment. The SINA panel recommends the following strategies for asthma treatment:
A controller medication is recommended for all steps. ICS is considered the most effective controller and the cornerstone of asthma treatment (Evidence A).[107],[108] Uncontrolled patients may require the addition of other controllersReliever medications must be available to patients at all steps. Increasing the use of reliever treatment should be considered as an early sign of worsening of asthma control (Evidence A).[109] The available relievers are as follows:A short-acting bronchodilator (SABA), such as salbutamol, is recommended to be taken as needed to relieve symptoms. Using SABA alone was found to increase the risk of asthma attacks and asthma-related death; therefore, asthma patients are not recommended to use it without being on a controller treatment; alternatively, ICS is recommended to be used whenever SABA is needed in Step 1[110],[111]Formoterol/ICS combination could be used as a reliever therapy on “as-needed basis” as per physician prescription. Formoterol is a long-acting bronchodilator (LABA) with fast-acting bronchodilator effect (Evidence A).[112],[113],[114] For Steps 3–5, it is only recommended when the combination of formoterol/ICS is prescribed as maintenance therapy. The maximum recommended dose of formoterol component is 72 mcg. Exceeding this level for 2–3 days may be a warning sign of deterioration of asthma control.[113],[114],[115]Regular assessment of adequate doses of treatment, proper technique, and adherenceRegular assessment of independent risk factors for acute asthma attacks in the past 12 months or prior history of admission to an ICU, especially if intubated.[79],[116] Other modifiable risk factors are recommended to be addressed, such as low initial FEV1, pregnancy, inadequate ICS, smoking and vaping, comorbidities, and major psychological conditionsRegular assessment of risk factors for fixed airway obstruction that includes inadequate ICS treatment, exposure to tobacco smoke or other noxious substances, low initial FEV1, or sputum/blood eosinophilia[117]Management of comorbidities with special attention to concomitant rhinosinusitis. As this condition affects asthma control, its treatment is expected to improve asthma outcome (Evidence A).[118],[119],[120] Treatment includes nasal saline washes, nasal steroids, leukotriene receptor antagonists (LTRAs), and antihistamines. Concomitant rhinosinusitis is recommended to be treated appropriately as well.Initiation of treatment
Patients with asthma often underestimate the presence of symptoms and tend to assume that their asthma is controlled even when this is not the case. Therefore, the consensus among the SINA panel is to simplify the approach and supplement the initiation of asthma therapy by utilizing an objective measurement with the ACT questionnaire [Box 4.2].[77] The following initial steps are recommended for treatment-naïve patients based on the ACT score [Box 6.1]:
Adjustment of treatment
After initiation of asthma treatment, it is recommended to assess the patient at 1–3 months' intervals (Evidence D).[125] The SINA panel recommends the utilization of stepwise approach of therapy to achieve asthma control. The stepwise approach consists of five steps as shown in [Box 6.2]. The SINA panel recommends that the stepwise approach is not meant to be compartmental; it is rather a continuum of care based on patient engagement and close monitoring of the disease (Evidence D).[126] In clinical practice, asthma severity can be retrospectively assessed based on the step of treatment required to control symptoms:[10],[81],[82],[83]
Reliever medications must be made available to patients at all steps. Increasing the use of reliever treatment is usually an early sign of asthma worsening (Evidence A).[109],[127] Approximately one in five patients with mild asthma may develop at least one attack of severe asthma in 12 months.[114],[128],[129] The available relievers are detailed above. The following paragraphs describe the asthma treatment at each step.
Treatment at step 1
Recommended option: Anti-inflammatory reliever therapy in the form of ICS/formoterol on as-needed basis (Evidence A).[114],[115],[121] Symptoms are usually mild and infrequent (usually < twice a month) with an ACT score of ≥20 and no risk factors for asthma attacksAlternative option: Use SABA together with low-dose ICS both on as-needed basis (Evidence B)[110],[111],[122]Patients with seasonal asthma who are symptomatic during the season are recommended to be treated with low-dose ICS before the beginning of the season (Evidence D).Treatment at step 2
Recommended optionsA daily low maintenance dose ICS with as-needed SABA (Evidence A)[107],[130]Combination of ICS/formoterol on “as-needed basis” (Evidence A).[113],[114] When compared to regular maintenance with low-dose ICS alone, it was found to be inferior with respect to controlling symptoms and noninferior with respect to the rate of severe asthma attacks and time to first attack. The combination of budesonide/formoterol on “as-needed basis” achieved such outcome with substantially lower ICS dose equivalent to 17%–25% of the maintenance dose of ICS.Alternative optionsLTRA (Montelukast) especially for those patients who are reluctant to use ICS or continue to have side effects, despite preventive measures (Evidence A).[131] LTRA is less effective than low-dose ICS in achieving asthma control and in reducing the risk of attacks.Maintenance of low-dose ICS could be recommended for patients who are controlled at the time of assessment (an ACT score of ≥20) but have risk factors for asthma attacks or fixed airway obstruction (Evidence B).[107],[126],[132],[133]Treatment at step 3
Combined low-dose ICS with LABA was found to improve asthma control for patient whose asthma is not controlled at step 2 and reduce asthma attacks (Evidence A).[134],[135] The patient is recommended to continue on reliever treatment on “as-needed basis” (Evidence A). ICS with LABA are available (refer Medication Appendix) as follows:
ICS combined with formoterol can be used as maintenance and reliever without adding SABAICSs in the form of beclomethasone dipropionate, budesonide, or fluticasone propionate are available in combination with salmeterol. These are normally prescribed twice daily with SABA as a relieverOnce-a-day combination of ICS and LABA (fluticasone furoate with vilanterol) is also available. SABA should be utilized as a reliever.Inhaled LABA alone is not available in the Saudi market since it should never be used alone in asthma management.[136] Asthma patients taking inhaled LABA without inhaled ICS are at an increased risk of asthma attacks, hospitalizations, and death.[137]
Recommended optionsIf a formoterol/ICS combination is prescribed, it is recommended to be used as maintenance with 1–2 inhalations twice daily. Extra doses up to 12 inhalations per day can be used as the reliever therapy from the same device (Evidence A).[110],[111],[112],[122] Those patients who require such high doses for 2–3 days should seek medical advice to step up maintenance therapy, and they may require the use of a short course of oral prednisolone (Evidence A)[112]If salmeterol/ICS combination is selected, an escalation of the regular daily doses to maximum dosing achieves asthma control in a majority of patients on uncontrolled at Steps 2 and 3 (Evidence A).[138] Salmeterol has a slow onset of action; therefore, it should only be used as a maintenance treatment with SABA as a relieverThe once-a-day combination of ICS/LABA in the form of fluticasone furoate/vilanterol (Relvar) can be prescribed at a daily inhalation dose of 100/25 mcg for adults and children above 12 years (Evidence A).[139],[140] As vilanterol has an onset of action within 15 min and a long half-life, it can only be used as a maintenance treatment while continuing SABA as a reliever.Alternative optionsThe continuation of ICS as a monotherapy by increasing the dose to the medium level is generally less effective strategy (Evidence A)[141],[142]The addition of LTRA to a low–medium-dose ICS is another option, especially in patients with concomitant rhinitis (Evidence A)[143],[144],[145]Tiotropium is a long-acting anticholinergic (antimuscarinic) agent (LAMA) approved for the treatment of COPD.[146],[147],[148] Evidence has shown that when tiotropium is added to an ICS, it improves symptoms, reduces risk of attack, and improves the lung function in patients with inadequately controlled asthma. Its effect appears to be at least equivalent to LABA (Evidence A).[149],[150],[151] This evidence supports that tiotropium can be combined with ICS whenever LABA cannot be used.[152]Consultation with an asthma specialist is recommended whenever there is a difficulty in achieving control at step 3 (Evidence D).Treatment at step 4
Consultation with an asthma specialist is recommended for patients who require this step of therapy (Evidence D).[153]
Treatment at step 5
Early consideration of biological therapy may save the patient from frequent or chronic use of OCSs and reduce asthma attacks. This therapy is recommended to be considered based on appropriate indications and availability. When choosing a biological agent, several factors should be considered including the frequency of administration, cost, side effect profile, age at onset of asthma, and presence of comorbid conditions, such as nasal polyps, previous response, and physician experience with the treatment. Consultation with an asthma specialist is strongly recommended for patients requiring treatment at step 5 (Evidence D). The following biological agents are available for step 5:
Anti-IgE therapy (Omalizumab) is recommended for those patients uncontrolled on maximum treatment at step 4, who have allergic asthma as determined by a positive skin test or RAST study and IgE level within the appropriate therapeutic range (for more information refer Medication Appendix, Medications Section) (Evidence A). A history of documented atopy might be used as a marker of allergic asthma if RAST test and skin test are unavailable (Evidence D).[142],[144],[154] During the course of therapy, anti-IgE led to more reduction of asthma attacks in a category of asthma patients who showed >50% reduction in blood eosinophils.[165],[166] The dose is determined by the IgE level and weight. If this treatment does not control asthma after 16 weeks of therapy, it should be stopped[167],[168],[169]Anti-IL-5 therapy can be considered for uncontrolled eosinophilic asthma or ≥2 attacks in the past 12 months requiring systemic corticosteroids at step 4 (for more information refer to Medication Appendix).[170] There are no data to determine the duration before deciding on treatment ineffectiveness. However, until this evidence is available, the treatment may be continued for up to 6 months before the decision of stopping/switching treatment (Evidence D).[171] The available options are as follows:Mepolizumab, an anti-IL-5 therapy, that is indicated when blood eosinophils count is ≥150 cells/μL at treatment initiation or ≥300 cells/μL at any time in the prior 12 months. The recommended dose is 100 mg subcutaneously every 4 weeksBenralizumab, an anti-IL-5 receptor therapy, that is indicated when blood eosinophils count at initiation of treatment is ≥300 cells/μL or ≥150 cells/μL for patients with prolonged OCS.[172] The recommended dose is 30 mg subcutaneously every 4 w
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