research articles on asthma

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• Published: 15 August 2020

Treatment strategies for asthma: reshaping the concept of asthma management

• Alberto Papi 1 , 7 ,
• Francesco Blasi 2 , 3 ,
• Giorgio Walter Canonica 4 ,
• Luca Morandi 1 , 7 ,
• Luca Richeldi 5 &
• Andrea Rossi 6  

Allergy, Asthma & Clinical Immunology volume  16 , Article number:  75 ( 2020 ) Cite this article

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Asthma is a common chronic disease characterized by episodic or persistent respiratory symptoms and airflow limitation. Asthma treatment is based on a stepwise and control-based approach that involves an iterative cycle of assessment, adjustment of the treatment and review of the response aimed to minimize symptom burden and risk of exacerbations. Anti-inflammatory treatment is the mainstay of asthma management. In this review we will discuss the rationale and barriers to the treatment of asthma that may result in poor outcomes. The benefits of currently available treatments and the possible strategies to overcome the barriers that limit the achievement of asthma control in real-life conditions and how these led to the GINA 2019 guidelines for asthma treatment and prevention will also be discussed.

Asthma, a major global health problem affecting as many as 235 million people worldwide [ 1 ], is a common, non-communicable, and variable chronic disease that can result in episodic or persistent respiratory symptoms (e.g. shortness of breath, wheezing, chest tightness, cough) and airflow limitation, the latter being due to bronchoconstriction, airway wall thickening, and increased mucus.

The pathophysiology of the disease is complex and heterogeneous, involving various host-environment interactions occurring at various scales, from genes to organ [ 2 ].

Asthma is a chronic disease requiring ongoing and comprehensive treatment aimed to reduce the symptom burden (i.e. good symptom control while maintaining normal activity levels), and minimize the risk of adverse events such as exacerbations, fixed airflow limitation and treatment side effects [ 3 , 4 ].

Asthma treatment is based on a stepwise approach. The management of the patient is control-based; that is, it involves an iterative cycle of assessment (e.g. symptoms, risk factors, etc.), adjustment of treatment (i.e. pharmacological, non-pharmacological and treatment of modifiable risk factors) and review of the response (e.g. symptoms, side effects, exacerbations, etc.). Patients’ preferences should be taken into account and effective asthma management should be the result of a partnership between the health care provider and the person with asthma, particularly when considering that patients and clinicians might aim for different goals [ 4 ].

This review will discuss the rationale and barriers to the treatment of asthma, that may result in poor patient outcomes. The benefits of currently available treatments and the possible strategies to overcome the barriers that limit the achievement of asthma control in real-life situations will also be discussed.

The treatment of asthma: where are we? Evolution of a concept

Asthma control medications reduce airway inflammation and help to prevent asthma symptoms; among these, inhaled corticosteroids (ICS) are the mainstay in the treatment of asthma, whereas quick-relief (reliever) or rescue medicines quickly ease symptoms that may arise acutely. Among these, short-acting beta-agonists (SABAs) rapidly reduce airway bronchoconstriction (causing relaxation of airway smooth muscles).

National and international guidelines have recommended SABAs as first-line treatment for patients with mild asthma, since the Global Initiative for Asthma guidelines (GINA) were first published in 1995, adopting an approach aimed to control the symptoms rather than the underlying condition; a SABA has been the recommended rescue medication for rapid symptom relief. This approach stems from the dated idea that asthma symptoms are related to bronchial smooth muscle contraction (bronchoconstriction) rather than a condition concomitantly caused by airway inflammation. In 2019, the GINA guidelines review (GINA 2019) [ 4 ] introduced substantial changes overcoming some of the limitations and “weaknesses” of the previously proposed stepwise approach to adjusting asthma treatment for individual patients. The concept of an anti-inflammatory reliever has been adopted at all degrees of severity as a crucial component in the management of the disease, increasing the efficacy of the treatment while lowering SABA risks associated with patients’ tendency to rely or over-rely on the as-needed medication.

Until 2017, the GINA strategy proposed a pharmacological approach based on a controller treatment (an anti-inflammatory, the pillar of asthma treatment), with a SABA as an additional rescue intervention. The reliever, a short-acting bronc hodilator, was merely an addendum , a medication to be used in case the real treatment (the controller) failed to maintain disease control: SABAs effectively induce rapid symptom relief but are ineffective on the underlying inflammatory process. Based on the requirement to achieve control, the intensity of the controller treatment was related to the severity of the disease, varying from low-dose ICS to combination low-dose ICS/long-acting beta-agonist (LABA), medium-dose ICS/LABA, up to high-dose ICS/LABA, as preferred controller choice, with a SABA as the rescue medication. As a result, milder patients were left without any anti-inflammatory treatment and could only rely on SABA rescue treatment.

Poor adherence to therapy is a major limitation of a treatment strategy based on the early introduction of the regular use of controller therapy [ 5 ]. Indeed, a number of surveys have highlighted a common pattern in the use of inhaled medication [ 6 ], in which treatment is administered only when asthma symptoms occur; in the absence of symptoms, treatment is avoided as patients perceive it as unnecessary. When symptoms worsen, patients prefer to use reliever therapies, which may result in the overuse of SABAs [ 7 ]. Indirect evidence suggests that the overuse of beta-agonists alone is associated with increased risk of death from asthma [ 8 ].

In patients with mild persistent disease, low-dose ICS decreases the risk of severe exacerbations leading to hospitalization and improves asthma control [ 9 ]. When low-dose ICS are ineffective in controlling the disease (Step 3 of the stepwise approach), a combination of low-dose ICS with LABA maintenance was the recommended first-choice treatment, plus as-needed SABA [ 3 , 10 ]. Alternatively, the combination low-dose ICS/LABA (formoterol) was to be used as single maintenance and reliever treatment (SMART). The SMART strategy containing the rapid-acting formoterol was recommended throughout GINA Steps 3 to 5 based on solid clinical-data evidence [ 3 ].

The addition of a LABA to ICS treatment reduces both severe and mild asthma exacerbation rates, as shown in the one-year, randomized, double-blind, parallel-group FACET study [ 11 ]. This study focused on patients with persistent asthma symptoms despite receiving ICS and investigated the efficacy of the addition of formoterol to two dose levels of budesonide (100 and 400 µg bid ) in decreasing the incidence of both severe and mild asthma exacerbations. Adding formoterol decreased the incidence of both severe and mild asthma exacerbations, independent of ICS dose. Severe and mild exacerbation rates were reduced by 26% and 40%, respectively, with the addition of formoterol to the lower dose of budesonide; the corresponding reductions were 63% and 62%, respectively, when formoterol was added to budesonide at the higher dose.

The efficacy of the ICS/LABA combination was confirmed in the post hoc analysis of the FACET study, in which patients were exposed to a combination of formoterol and low-dose budesonide [ 12 ]. However, such high levels of asthma control are not achieved in real life [ 5 ]. An explanation for this is that asthma is a variable condition and this variability might include the exposure of patients to factors which may cause a transient steroid insensitivity in the inflammatory process. This, in turn, may lead to an uncontrolled inflammatory response and to exacerbations, despite optimal controller treatment. A typical example of this mechanism is given by viral infections, the most frequent triggers of asthma exacerbations. Rhinoviruses, the most common viruses found in patients with asthma exacerbations, interfere with the mechanism of action of corticosteroids making the anti-inflammatory treatment transiently ineffective. A transient increase in the anti-inflammatory dose would overcome the trigger-induced anti-inflammatory resistance, avoiding uncontrolled inflammation leading to an exacerbation episode [ 13 , 14 , 15 ].

Indeed, symptoms are associated with worsening inflammation and not only with bronchoconstriction. Romagnoli et al. showed that inflammation, as evidenced by sputum eosinophilia and eosinophilic markers, is associated with symptomatic asthma [ 16 ]. A transient escalation of the ICS dose would prevent loss of control over inflammation and decrease the risk of progression toward an acute episode. In real life, when experiencing a deterioration of asthma control, patients self-treat by substantially increasing their SABA medication (Fig.  1 ); it is only subsequently that they (modestly) increase the maintenance treatment [ 17 ].

Mean use of SABA at different stages of asthma worsening. Patients have been grouped according to maintenance therapy shown in the legend. From [ 17 ], modified

As bronchodilators, SABAs do not control the underlying inflammation associated with increased symptoms. The “as required” use of SABAs is not the most effective therapeutic option in controlling a worsening of inflammation, as signaled by the occurrence of symptoms; instead, an anti-inflammatory therapy included in the rescue medication along with a rapid-acting bronchodilator could provide both rapid symptom relief and control over the underlying inflammation. Thus, there is a need for a paradigm shift, a new therapeutic approach based on the rescue use of an inhaled rapid-acting beta-agonist combined with an ICS: an anti-inflammatory reliever strategy [ 18 ].

The symptoms of an exacerbation episode, as reported by Tattersfield and colleagues in their extension of the FACET study, increase gradually before the peak of the exacerbation (Fig.  2 ); and the best marker of worsening asthma is the increased use of rescue beta-agonist treatment that follows exactly the pattern of worsening symptomatology [ 19 ]. When an ICS is administered with the rescue bronchodilator, the patient would receive anti-inflammatory therapy when it is required; that is, when the inflammation is uncontrolled, thus increasing the efficiency of the anti-inflammatory treatment.

(From [ 19 ])

Percent variation in symptoms, rescue beta-agonist use and peak expiratory flow (PEF) during an exacerbation. In order to allow comparison over time, data have been standardized (Day-14 = 0%; maximum change = 100%)

Barriers and paradoxes of asthma management

A number of barriers and controversies in the pharmacological treatment of asthma have prevented the achievement of effective disease management [ 20 ]. O’Byrne and colleagues described several such controversies in a commentary published in 2017, including: (1) the recommendation in Step 1 of earlier guidelines for SABA bronchodilator use alone, despite asthma being a chronic inflammatory condition; and (2) the autonomy given to patients over perception of need and disease control at Step 1, as opposed to the recommendation of a fixed-dose approach with treatment-step increase, regardless of the level of symptoms [ 20 ]. Other controversies outlined were: (3) a difficulty for patients in understanding the recommendation to minimize SABA use at Step 2 and switch to a fixed-dose ICS regimen, when they perceive SABA use as more effective; (4) apparent conflicting safety messages within the guidelines that patient-administered SABA monotherapy is safe, but patient-administered LABA monotherapy is not; and (5) a discrepancy as to patients’ understanding of “controlled asthma” and their symptom frequency, impact and severity [ 20 ].

Controversies (1) and (2) can both establish an early over-dependence on SABAs. Indeed, asthma patients freely use (and possibly overuse) SABAs as rescue medication. UK registry data have recently suggested SABA overuse or overreliance may be linked to asthma-related deaths: among 165 patients on short-acting relievers at the time of death, 56%, 39%, and 4% had been prescribed > 6, > 12, and > 50 SABA inhalers respectively in the previous year [ 21 ]. Registry studies have shown the number of SABA canisters used per year to be directly related to the risk of death in patients with asthma. Conversely, the number of ICS canisters used per year is inversely related to the rate of death from asthma, when compared with non-users of ICS [ 8 , 22 ]. Furthermore, low-dose ICS used regularly are associated with a decreased risk of asthma death, with discontinuation of these agents possibly detrimental [ 22 ].

Other barriers to asthma pharmacotherapy have included the suggestion that prolonged treatment with LABAs may mask airway inflammation or promote tolerance to their effects. Investigating this, Pauwels and colleagues found that in patients with asthma symptoms that were persistent despite taking inhaled glucocorticoids, the addition of regular treatment with formoterol to budesonide for a 12-month period did not decrease asthma control, and improved asthma symptoms and lung function [ 11 ].

Treatment strategies across all levels of asthma severity

Focusing on risk reduction, the 2014 update of the GINA guidelines recommended as-needed SABA for Step 1 of the stepwise treatment approach, with low-dose ICS maintenance therapy as an alternative approach for long-term anti-inflammatory treatment [ 23 ]. Such a strategy was only supported by the evidence from a post hoc efficacy analysis of the START study in patients with recently diagnosed mild asthma [ 24 ]. The authors showed that low-dose budesonide reduced the decline of lung-function over 3 years and consistently reduced severe exacerbations, regardless of symptom frequency at baseline, even in subjects with symptoms below the then-threshold of eligibility for ICS [ 24 ]. However, as for all post hoc analyses, the study by Reddel and colleagues does not provide conclusive evidence and, even so, their results could have questionable clinical significance for the management of patients with early mild asthma. To be effective, this approach would require patients to be compliant to regular twice-daily ICS for 10 years to have the number of exacerbations reduce by one. In real life, it is highly unlikely that patients with mild asthma would adhere to such a regular regimen [ 25 ].

The 2016 update to the GINA guidelines lowered the threshold for the use of low-dose ICS (GINA Step 2) to two episodes of asthma symptoms per month (in the absence of any supportive evidence for the previous cut-off). The objective was to effectively increase the asthma population eligible to receive regular ICS treatment and reduce the population treated with a SABA only, given the lack of robust evidence of the latter’s efficacy and safety and the fact that asthma is a variable condition characterized by acute exacerbations [ 26 ]. Similarly, UK authorities recommended low-dose ICS treatment in mild asthma, even for patients with suspected asthma, rather than treatment with a SABA alone [ 10 ]. However, these patients are unlikely to have good adherence to the regular use of an ICS. It is well known that poor adherence to treatment is a major problem in asthma management, even for patients with severe asthma. In their prospective study of 2004, Krishnan and colleagues evaluated the adherence to ICS and oral corticosteroids (OCS) in a cohort of patients hospitalized for asthma exacerbations [ 27 ]. The trend in the data showed that adherence to ICS and OCS treatment in patients dropped rapidly to reach nearly 50% within 7 days of hospital discharge, with the rate of OCS discontinuation per day nearly double the rate of ICS discontinuation per day (− 5.2% vs. − 2.7%; p < 0.0001 respectively, Fig.  3 ), thus showing that even after a severe event, patients’ adherence to treatment is suboptimal [ 27 ].

(From [ 27 ])

Use of inhaled (ICS) and oral (OCS) corticosteroids in patients after hospital discharge among high-risk adult patients with asthma. The corticosteroid use was monitored electronically. Error bars represent the standard errors of the measured ICS and OCS use

Guidelines set criteria with the aim of achieving optimal control of asthma; however, the attitude of patients towards asthma management is suboptimal. Partridge and colleagues were the first in 2006 to evaluate the level of asthma control and the attitude of patients towards asthma management. Patients self-managed their condition using their medication as and when they felt the need, and adjusted their treatment by increasing their intake of SABA, aiming for an immediate relief from symptoms [ 17 ]. The authors concluded that the adoption of a patient-centered approach in asthma management could be advantageous to improve asthma control.

The concomitant administration of an as-needed bronchodilator and ICS would provide rapid relief while administering anti-inflammatory therapy. This concept is not new: in the maintenance and reliever approach, patients are treated with ICS/formoterol (fast-acting, long-acting bronchodilator) combinations for both maintenance and reliever therapy. An effective example of this therapeutic approach is provided in the SMILE study in which symptomatic patients with moderate to severe asthma and treated with budesonide/formoterol as maintenance therapy were exposed to three different as-needed options: SABA (terbutaline), rapid-onset LABA (formoterol) and a combination of LABA and ICS (budesonide/formoterol) [ 28 ]. When compared with formoterol, budesonide/formoterol as reliever therapy significantly reduced the risk of severe exacerbations, indicating the efficacy of ICS as rescue medication and the importance of the as-needed use of the anti-inflammatory reliever.

The combination of an ICS and a LABA (budesonide/formoterol) in one inhaler for both maintenance and reliever therapy is even more effective than higher doses of maintenance ICS and LABA, as evidenced by Kuna and colleagues and Bousquet and colleagues (Fig.  4 ) [ 29 , 30 ].

(Data from [ 29 , 30 ])

Comparison between the improvements in daily asthma control resulting from the use of budesonide/formoterol maintenance and reliever therapy vs. higher dose of ICS/LABA + SABAZ and steroid load for the two regimens

The effects of single maintenance and reliever therapy versus ICS with or without LABA (controller therapy) and SABA (reliever therapy) have been recently addressed in the meta-analysis by Sobieraj and colleagues, who analysed 16 randomized clinical trials involving patients with persistent asthma [ 31 ]. The systematic review supported the use of single maintenance and reliever therapy, which reduces the risk of exacerbations requiring systemic corticosteroids and/or hospitalization when compared with various strategies using SABA as rescue medication [ 31 ].

This concept was applied to mild asthma by the BEST study group, who were the first to challenge the regular use of ICS. A pilot study by Papi and colleagues evaluated the efficacy of the symptom-driven use of beclomethasone dipropionate plus albuterol in a single inhaler versus maintenance with inhaled beclomethasone and as-needed albuterol. In this six-month, double-blind, double-dummy, randomized, parallel-group trial, 455 patients with mild asthma were randomized to one of four treatment groups: an as-needed combination therapy of placebo bid plus 250 μg of beclomethasone and 100 μg of albuterol in a single inhaler; an as-needed albuterol combination therapy consisting of placebo bid plus 100 μg of albuterol; regular beclomethasone therapy, comprising beclomethasone 250 μg bid and 100 μg albuterol as needed); and regular combination therapy with beclomethasone 250 μg and albuterol 100 μg in a single inhaler bid plus albuterol 100 μg as needed.

The rescue use of beclomethasone/albuterol in a single inhaler was as efficacious as the regular use of inhaled beclomethasone (250 μg bid ) and it was associated with a lower 6-month cumulative dose of the ICS [ 32 ].

The time to first exacerbation differed significantly among groups ( p  = 0.003), with the shortest in the as-needed albuterol and placebo group (Fig.  5 ). Figure  5 also shows equivalence between the as-needed combination therapy and the regular beclomethasone therapy. However, these results were not conclusive since the study was not powered to evaluate the effect of the treatment on exacerbations. In conclusion, as suggested by the study findings, mild asthma patients may require the use of an as-needed ICS and an inhaled bronchodilator rather than a regular treatment with ICS [ 32 ].

(From [ 32 ])

Kaplan Meier analysis of the time to first exacerbation (modified intention-to-treat population). First asthma exacerbations are shown as thick marks. As-needed albuterol therapy = placebo bid plus 100 μg of albuterol as needed; regular combination therapy = 250 μg of beclomethasone and 100 μg of albuterol in a single inhaler bid plus 100 μg of albuterol as needed; regular beclomethasone therapy = 250 μg of beclomethasone bid and 100 μg of albuterol as needed; as-needed combination therapy = placebo bid plus 250 μg of beclomethasone and 100 μg of albuterol in a single inhaler as needed

Moving forward: a new approach to the management of asthma patients

Nearly a decade after the publication of the BEST study in 2007, the use of this alternative therapeutic strategy was addressed in the SYGMA 1 and SYGMA 2 trials. These double-blind, randomized, parallel-group, 52-week phase III trials evaluated the efficacy of as-needed use of combination formoterol (LABA) and the ICS budesonide as an anti-inflammatory reliever in patients requiring GINA Step 2 treatment, with the current reliever therapy (e.g. as-needed SABA) or with low-dose maintenance ICS (inhaled budesonide bid ) plus as-needed SABA, administered as regular controller therapy [ 33 , 34 ].

The SYGMA 1 trial, which enrolled 3849 patients, aimed to demonstrate the superiority of the as-needed use of the combination budesonide/formoterol over as-needed terbutaline, as measured by the electronically-recorded proportion of weeks with well-controlled asthma [ 34 ]. The more pragmatic SYGMA 2 trial enrolled 4215 patients with the aim to demonstrate that the budesonide/formoterol combination is non-inferior to budesonide plus as-needed terbutaline in reducing the relative rate of annual severe asthma exacerbations [ 33 ]. Both trials met their primary efficacy outcomes. In particular, as-needed budesonide/formoterol was superior to as-needed SABA in controlling asthma symptoms (34.4% versus 31.1%) and preventing exacerbations, achieving a 64% reduction in exacerbations. In both trials, budesonide/formoterol as-needed was similar to budesonide maintenance bid at preventing severe exacerbations, with a substantial reduction of the inhaled steroid load over the study period (83% in the SYGMA 1 trial and 75% in the SYGMA 2 trial). The time to first exacerbation did not differ significantly between the two regimens; however, budesonide/formoterol was superior to SABA in prolonging the time to first severe exacerbation [ 33 , 34 ].

The double-blind, placebo-controlled design of the SYGMA trials does not fully address the advantages of anti-inflammatory reliever strategy in patients who often rely on SABAs for symptom relief, so to what extent the study findings could apply to real-life practice settings was unclear.

These limitations were overcome by the results of the Novel START study, an open-label, randomized, parallel-group, controlled trial designed to reflect real-world practice, which demonstrated the effectiveness in mild asthma of budesonide/formoterol as an anti-inflammatory reliever therapy [ 35 ].

In real-world practice, mild asthma patients are treated with an as-needed SABA reliever or with daily low-dose ICS maintenance therapy plus a SABA reliever. In the Novel START study, 668 patients with mild asthma were randomized to receive either as-needed albuterol 100 µg, two inhalations (SABA reliever as a continuation of the Step 1 treatment according to the 2017 GINA guidelines), budesonide 200 µg (ICS maintenance treatment) plus as-needed albuterol (Step 2 therapy of the GINA 2017 guidelines), or 200 µg/6 µg budesonide/formoterol as anti-inflammatory reliever therapy taken as-needed for a 52-week study period.

In this study, the rate of asthma exacerbations for budesonide/formoterol was lower compared with albuterol (51%) and similar to the twice-daily maintenance budesonide plus albuterol, despite a 52% reduction in the mean steroid dose with the single combination inhaler treatment [ 35 ]. In addition, severe exacerbation rate was lower with budesonide/formoterol as compared with as-needed albuterol and regular twice-daily budesonide. These data support the findings of the SYGMA 1 and 2 trials, highlighting the need for a critical re-examination of current clinical practice. Along with the results of the SYGMA trials, they provide convincing evidence of the advantages of the anti-inflammatory reliever strategy, particularly in real-life settings.

The SYGMA 1, SYGMA 2 and the novel START studies complete the picture of the treatment strategies for asthma at any degree of severity, including mild asthma. A growing body of evidence shows that an anti-inflammatory reliever strategy, when compared with all other strategies with SABA reliever, consistently reduces the rate of exacerbations across all levels of asthma severity (Fig.  6 ) [ 28 , 29 , 34 , 36 , 37 , 38 , 39 ].

(Data source: [ 39 ])

Risk reduction of severe asthma attack of anti-inflammatory reliever versus SABA across all levels of asthma severity. Bud = budesonide; form = formoterol; TBH = turbohaler. Data from: 1: [ 36 ]; 2: [ 37 ]; 3: [ 38 ]; 4: [ 28 ]; 5: [ 29 ]; 6: [ 30 ]; 7: [ 34 ]

This evidence set the ground (Fig.  7 ) for the release of the 2019 GINA strategy updates. The document provides a consistent approach towards the management of the disease and aims to avoid the overreliance and overuse of SABAs, even in the early course of the disease. The 2019 GINA has introduced key changes in the treatment of mild asthma: for safety reasons, asthmatic adults and adolescents should receive ICS-containing controller treatment instead of the SABA-only treatment, which is no longer recommended.

Timeline of key randomized controlled trials and meta-analyses providing the supporting evidence base leading to the Global Initiative for Asthma (GINA) 2019 guidelines. GINA global initiative for asthma, MART maintenance and reliever therapy, SMART single inhaler maintenance and reliever therapy

In Step 1 of the stepwise approach to adjusting asthma treatment, the preferred controller option for patients with fewer than two symptoms/month and no exacerbation risk factors is low-dose ICS/formoterol as needed. This strategy is indirectly supported by the results of the SYGMA 1 study which evaluated the efficacy and safety of budesonide/formoterol as needed, compared with as-needed terbutaline and budesonide bid plus as-needed terbutaline (see above). In patients with mild asthma, the use of an ICS/LABA (budesonide/formoterol) combination as needed provided superior symptom control to as-needed SABA, resulting in a 64% lower rate of exacerbations (p = 0.07) with a lower steroid dose (17% of the budesonide maintenance dose) [ 34 ]. The changes extend to the other controller options as well. In the 2017 GINA guidelines, the preferred treatment was as-needed SABA with the option to consider adding a regular low-dose ICS to the reliever. In order to overcome the poor adherence with the ICS regimen, and with the aim to reduce the risk of severe exacerbations, the 2019 GINA document recommends taking low-dose ICS whenever SABA is taken, with the daily ICS option no longer listed.

Previous studies including the TREXA study in children and adolescents [ 40 ], the BASALT study [ 41 ] and research conducted by the BEST study group [ 32 ] have already added to the evidence that a low-dose ICS with a bronchodilator is an effective strategy for symptom control in patients with mild asthma. A recently published study in African-American children with mild asthma found that the use of as-needed ICS with SABA provides similar asthma control, exacerbation rates and lung function measures at 1 year, compared with daily ICS controller therapy [ 42 ], adding support to TREXA findings that in children with well controlled, mild asthma, ICS used as rescue medication with SABA may be an efficacious step-down strategy [ 40 ].

In Step 2 of the stepwise approach, there are now two preferred controller options: (a) a daily low-dose ICS plus an as-needed SABA; and (b) as-needed low-dose ICS/formoterol. Recommendation (a) is supported by a large body of evidence from randomized controlled trials and observations showing a substantial reduction of exacerbation, hospitalization, and death with regular low-dose ICS [ 7 , 8 , 9 , 24 , 43 ], whereas recommendation (b) stems from evidence on the reduction or non-inferiority for severe exacerbations when as-needed low-dose ICS/formoterol is compared with regular ICS [ 33 , 34 ].

The new GINA document also suggests low-dose ICS is taken whenever SABA is taken, either as separate inhalers or in combination. This recommendation is supported by studies showing reduced exacerbation rates compared with taking a SABA only [ 32 , 40 ], or similar rates compared with regular ICS [ 32 , 40 , 41 ]. Low-dose theophylline, suggested as an alternative controller in the 2017 GINA guidelines, is no longer recommended.

Airway inflammation is present in the majority of patients with asthma, and although patients with mild asthma may have only infrequent symptoms, they face ongoing chronic inflammation of the lower airways and risk acute exacerbations. The GINA 2019 strategy recognizes the importance of reducing the risk of asthma exacerbations, even in patients with mild asthma (Steps 1 and 2) [ 4 ]. In this regard, the new recommendations note that SABA alone for symptomatic treatment is non-protective against severe exacerbation and may actually increase exacerbation risk if used regularly or frequently [ 4 ].

The reluctance by patients to regularly use an ICS controller means they may instead try and manage their asthma symptoms by increasing their SABA reliever use. This can result in SABA overuse and increased prescribing, and increased risk of exacerbations.

As part of the global SABINA (SABA use IN Asthma) observational study programme, a UK study examined primary care records to describe the pattern of SABA and ICS use over a 10-year period in 373,256 patients with mild asthma [ 44 ]. Results showed that year-to-year SABA prescribing was more variable than that of ICS indicating that, in response to fluctuations in asthma symptom control, SABA use was increased in preference to ICS use. Furthermore, more than 33% of patients were prescribed SABA inhalers at a level equivalent to around ≥ 3 puffs per week which, according to GINA, suggests inadequate asthma control.

The problem of SABA overuse is further highlighted by two studies [ 45 , 46 ], also as part of the SABINA programme. These analysed data from 365,324 patients in a Swedish cohort prescribed two medications for obstructive lung disease in any 12-month period (HERA).

The first study identified SABA overuse (defined as ≥ 3 SABA canisters a year) in 30% of patients, irrespective of their ICS use; 21% of patients were collecting 3–5 canisters annually, 7% were collecting 6–10, and 2% more than 11 [ 45 ]. Those patients who were overusing SABA had significantly more asthma exacerbations relative to those using < 3 canisters (20.0 versus 12.5 per 100 patient years; relative risk 1.60, 95% CI 1.57–1.63, p < 0.001). Moreover, patients overusing SABA and whose asthma was more severe (GINA Steps 3 and 4) had greater exacerbation risk compared with overusing patients whose asthma was milder (GINA Steps 1 and 2).

The second study found those patients using three or more SABA reliever canisters a year had an increased all-cause mortality risk relative to patients using fewer SABA canisters: hazard ratios after adjustment were 1.26 (95% CI 1.14–1.39) for 3–5 canisters annually, 1.67 (1.49–1.87) for 6–10 canisters, and 2.35 (2.02–2.72) for > 11 canisters, relative to patients collecting < 3 canisters annually [ 46 ].

The recently published PRACTICAL study lends further support to as-needed low-dose ICS/formoterol as an alternative option to daily low-dose ICS plus as-needed SABA, outlined in Step 2 of the guidelines [ 47 ]. In their one-year, open-label, multicentre, randomized, superiority trial in 890 patients with mild to moderate asthma, Hardy and colleagues found that the rate of severe exacerbations per patient per year (the primary outcome) was lower in patients who received as-needed budesonide/formoterol than in patients who received controller budesonide plus as-needed terbutaline (relative rate 0.69, 95% CI 0.48–1.00; p < 0.05). Indeed, they suggest that of these two treatment options, as-needed low-dose ICS/formoterol may be preferred over controller low-dose ICS plus as-needed SABA for the prevention of severe exacerbations in this patient population.

Step 3 recommendations have been left unchanged from 2017, whereas Step 4 treatment has changed from recommending medium/high-dose ICS/LABA [ 3 ] to medium-dose ICS/LABA; the high-dose recommendation has been escalated to Step 5. Patients who have asthma that remains uncontrolled after Step 4 treatment should be referred for phenotypic assessment with or without add-on therapy.

To summarise, the use of ICS medications is of paramount importance for optimal asthma control. The onset and increase of symptoms are indicative of a worsening inflammation leading to severe exacerbations, the risk of which is reduced by a maintenance plus as-needed ICS/LABA combination therapy. The inhaled ICS/bronchodilator combination is as effective as the regular use of inhaled steroids.

The efficacy of anti-inflammatory reliever therapy (budesonide/formoterol) versus current standard-of-care therapies in mild asthma (e.g. reliever therapy with a SABA as needed and regular maintenance controller therapy plus a SABA as-needed) has been evaluated in two randomized, phase III trials which confirmed that, with respect to as-needed SABA, the anti-inflammatory reliever as needed is superior in controlling asthma and reduces exacerbation rates, exposing the patients to a substantially lower glucocorticoid dose.

Conclusions

A growing body of evidence shows that anti-inflammatory reliever strategy is more effective than other strategies with SABA reliever in controlling asthma and reducing exacerbations across all levels of asthma severity. A budesonide/formoterol therapy exposes asthma patients to a substantially lower glucocorticoid dose while cutting the need for adherence to scheduled therapy.

Availability of data and materials

Not applicable.

Abbreviations

Global Initiative for Asthma

Inhaled corticosteroids

Long-acting beta-agonists

Oral corticosteroids

Short-acting beta-agonists

Single inhaler maintenance and reliever treatment

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Acknowledgements

The Authors thank Maurizio Tarzia and Gayle Robins, independent medical writers who provided editorial assistance on behalf of Springer Healthcare Communications. The editorial assistance was funded by AstraZeneca.

No funding was received for this study. The editorial assistance was funded by AstraZeneca.

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Papi, A., Blasi, F., Canonica, G.W. et al. Treatment strategies for asthma: reshaping the concept of asthma management. Allergy Asthma Clin Immunol 16 , 75 (2020). https://doi.org/10.1186/s13223-020-00472-8

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• Continuing Education Activity

Asthma is a chronic inflammatory respiratory condition characterized by hallmark symptoms of intermittent dyspnea, cough, and wheezing. However, due to the nonspecific nature of these symptoms, distinguishing asthma from other respiratory illnesses can sometimes be challenging. A confirmed diagnosis of asthma relies on consistent respiratory symptoms and the identification of variable expiratory airflow obstruction documented on spirometry. Clinicians prioritize symptom control and prevention of future exacerbations through tailored treatment, considering symptom frequency, severity, and potential risks in a step-wise approach. Early recognition and intervention of asthma exacerbations are crucial to prevent the progression of asthma to severe, life-threatening stages. Fatalities related to asthma highlight missed opportunities in recognizing disease severity and escalating therapy, emphasizing the critical role of continual patient education and routine symptom control assessment for successful long-term management. 

The development of asthma, often presenting in childhood, involves a complex interplay of genetic and environmental factors associated with atopy. Researchers strive to develop predictive systems for identifying individuals at risk of continued symptoms into adulthood. Despite significant advancements in understanding the underlying genetic loci, environmental triggers, and risk factors, clinical strategies remain lacking to mitigate the risks of persistent asthma development into adolescence and adulthood. This activity covers the epidemiology, pathophysiology, and assessment of asthma, along with initiating pharmacological treatment and developing monitoring strategies tailored for adolescents and adults. These strategies closely align with evidence-based recommendations from the National Asthma Education and Prevention Program and the Global Initiative for Asthma.

• Identify the hallmark symptoms of asthma, including dyspnea, cough, and wheezing.
• Implement evidence-based treatment strategies for asthma management, considering individual patient characteristics and preferences.
• Assess asthma severity, control, and exacerbation risk regularly during follow-up visits.
• Collaborate with interdisciplinary healthcare team members to optimize asthma care and patient outcomes.
• Introduction

Asthma is a prevalent chronic inflammatory respiratory condition affecting millions of people worldwide and presents substantial challenges in both diagnosis and management. This respiratory condition is characterized by inflammation of the airways, causing intermittent airflow obstruction and bronchial hyperresponsiveness. The hallmark asthma symptoms include coughing, wheezing, and shortness of breath, which can be frequently exacerbated by triggers ranging from allergens to viral infections. The prevalence and severity of asthma are determined by a complex interplay between genetic and environmental factors. Despite treatment advancements, disparities persist in asthma care, with variations in access to diagnosis, treatment, and patient education across different demographics.

The development of asthma, often presenting in childhood, is associated with other atopic features, such as eczema and hay fever. [1] [2] [3]  Severity varies from intermittent symptoms to life-threatening airway closure. Healthcare professionals establish a definitive diagnosis through patient history, physical examination, pulmonary function testing, and appropriate laboratory testing. Spirometry with a post-bronchodilator response (BDR) is the primary diagnostic test. Treatment focuses on providing continued education, routine symptom assessment, access to fast-acting bronchodilators, and appropriate controller medications tailored to disease severity.

Asthma manifests with diverse phenotypes, likely influenced by intricate interactions between genetic and environmental factors. [4] [5]  Genomewide association studies have linked childhood-onset asthma to markers near the ORMDL sphingolipid biosynthesis regulator 3 ( ORMDL3 ) and gasdermin B ( GSDMB ) genes on chromosome 17q21, encoding ORM1-like protein 3 and gasdermin-like protein. [6]  Other associations include genes such as interleukin-33 ( IL33 ), IL-1 receptor-like 1 ( IL1R1 ) genes, and a novel susceptibility locus at the IF-inducible protein X ( PYHIN1 ) gene, particularly affecting individuals of African descent. [7]  

The EVE Consortium also identifies a susceptibility locus for thymic stromal lymphopoietin ( TSLP ), an epithelial cell–derived cytokine implicated in asthma-related inflammation initiation. [8]  Asthma patients exhibit higher TSLP expression in their airways compared to healthy controls. Additional genetic loci involved in asthma include major histocompatibility complex class II DQ α1 ( HLA-DQA1 ), HLA-DQB1 antisense RNA 1 ( HLA-DQB1 ), Toll-like receptor 1 ( TLR1 ), IL-6 receptor ( IL6R ), zona pellucida-binding protein 2 ( ZPBP2 ), and gasdermin A ( GSDMA ).

Genetics may also be pivotal in asthma treatment. The hydroxy-δ-5-steroid dehydrogenase, 3-beta- and steroid δ-isomerase 1 ( HSD3B1 ) genotype is associated with glucocorticoid resistance among patients. In addition, single-nucleotide polymorphisms in protein kinase cGMP-dependent 1 ( PRKG1 )   and SPATA13 antisense RNA 1 ( SPATA13-AS1 )   are associated with BDR in Black children. [9]

Differing concordance rates among monozygotic twins suggest that exposure to environmental factors has an essential role in the development of asthma. Specific alleles have different effects depending on the environmental exposures. For example, exposure to secondhand smoke associates variations in the  N -acetyltransferase 1 ( NAT1 ) gene with the development of asthma in children. A study involving 983 children with single-nucleotide polymorphisms related to  ORMDL3  and  GSDMB  at chromosome locus 17q21 reveals that the same genotype poses genetic risk while also offering environmental protection. [10]

Risk Factors

Risk factors for asthma development encompass exposures throughout a patient's lifespan, including the perinatal period. The most substantial known risk factor is atopy, which is characterized by the genetic tendency to produce specific immunoglobulin E (IgE) antibodies in response to common environmental allergens. Nearly one-third of children with atopy will develop asthma later in life. 

Prenatal and Perinatal Factors

Prematurity is the most crucial risk factor influencing asthma incidence during this period. [11] [12] [13] [14]  Preterm birth, occurring before 36 weeks, is associated with an elevated risk of asthma throughout childhood, adolescence, and adulthood. Researchers posit that impaired lung development in preterm infants, even in those without early respiratory complications, increases the long-term risk of asthma. [15] Exposure to maternal smoking during pregnancy causes diminished pulmonary function in newborns and an increased probability of developing childhood asthma. Moreover, smoking during pregnancy correlates with several adverse pregnancy outcomes, including premature delivery, further elevating the asthma risk.

The incidence of childhood asthma increases with a maternal age of 20 or younger and decreases with a maternal age of 30 or older. Maternal diet during pregnancy holds significance, with researchers suggesting that vitamin D deficiency contributes to early-life wheezing and asthma primarily by impacting the immune function of various cell types, notably dendritic and T regulatory cells. Additionally, vitamin D plays a role in fetal lung development. [16] [17]  Although some studies present conflicting findings regarding the association between maternal vitamin D levels and childhood asthma, a meta-analysis of 2 large studies indicates that maternal vitamin D intake offers protection against wheezing or asthma in offspring up to the age of 3. [16]  

The Copenhagen Prospective Studies on Asthma in Childhood (COPSAC2010) reveals that 17% of children born to mothers with diets high in omega-3 polyunsaturated fatty acids developed persistent wheeze or asthma during the first 3 years of life compared to nearly 24% in the group with diets high in omega-6 polyunsaturated fatty acids. Vitamins E and C and zinc may also have protective effects. Administering vitamin C at a dose of 500 mg/d to pregnant mothers appears to offer protection against the harmful effects of tobacco exposure. Offspring of mothers who receive vitamin C supplementation exhibit a wheezing incidence of 28%, while those without vitamin C supplementation have a higher incidence of 47%. [18] [19]

Wheezing caused by viral infections, particularly respiratory syncytial virus and human rhinovirus, may predispose infants and young children to develop asthma later in life. In addition, early-life exposure to air pollution, including combustion by-products from gas-fired appliances and indoor fires, obesity, and early puberty, also increases the risk of asthma. 

The most significant risk factors for adult-onset asthma include tobacco smoke, occupational exposure, and adults with rhinitis or atopy. Studies also suggest a modest increase in asthma incidence among postmenopausal women taking hormone replacement therapy. 

Furthermore, the following factors can contribute to asthma and airway hyperreactivity:

• Exposure to environmental allergens such as house dust mites, animal allergens (especially from cats and dogs), cockroach allergens, and fungi
• Physical activity or exercise
• Conditions such as hyperventilation, gastroesophageal reflux disease, and chronic sinusitis
• Hypersensitivity to aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs), as well as sulfite sensitivity
• Use of β-adrenergic receptor blockers, including ophthalmic preparations
• Exposure to irritants such as household sprays and paint fumes
• Contact with various high- and low-molecular-weight compounds found in insects, plants, latex, gums, diisocyanates, anhydrides, wood dust, and solder fluxes, which are associated with occupational asthma
• Emotional factors or stress

Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease   (AERD) is a condition characterized by a combination of asthma, chronic rhinosinusitis with nasal polyposis, and NSAID intolerance. Patients with AERD present with upper and lower respiratory tract symptoms after ingesting aspirin or NSAIDs that inhibit cyclooxygenase-1 (COX-1). This condition arises from dysregulated arachidonic acid metabolism and the overproduction of leukotrienes involving the 5-lipoxygenase and cyclooxygenase pathways. AERD affects approximately 7% of adults with asthma.

Occupational-Induced Asthma

Two types of occupational asthma exist based on their appearance after a latency period: 

• Occupational asthma triggered by workplace sensitizers results from an allergic or immunological process associated with a latency period induced by both low- and high-molecular-weight agents. High-molecular-weight substances, such as flour, contain proteins and polysaccharides of plant or animal origin. Low-molecular-weight substances, like formaldehyde, form a sensitizing neoantigen when combined with a human protein.
• Occupational asthma caused by irritants involves a   nonallergic or nonimmunological process induced by gases, fumes, smoke, and aerosols.
• Epidemiology

The worldwide incidence of asthma is estimated to affect 260 million individuals. [20] Recent studies examining asthma prevalence across 17 countries reveal varying rates, ranging from 3.4% to 6% for adults and children in India, Taiwan, Kosovo, Nigeria, and Russia, and higher rates of 17% to 33% for Honduras, Costa Rica, Brazil, and New Zealand. [21]  Despite data showing the death rate consistently declining for asthma between 2001 and 2015, asthma continues to account for approximately 420,000 deaths per year. [22]  Factors such as under-prescription of inhaled glucocorticoids and limited access to emergency medical care or specialist care all play a role in asthma-related deaths.

Asthma prevalence in the United States differs among demographic groups, including age, gender, race, and socioeconomic status. The United States Centers for Disease Control and Prevention (CDC) estimates that around 25 million Americans are currently affected by asthma. Among individuals younger than 18, boys exhibit a higher prevalence compared to girls, while among adults, women are more commonly affected than men. Additionally, asthma prevalence is notably higher among Black individuals, with a prevalence of 10.1%, compared to White individuals at 8.1%. Hispanic Americans generally have a lower prevalence of 6.4%, except for those from Puerto Rico, where the prevalence rises to 12.8%. Moreover, underrepresented minorities and individuals living below the poverty line experience the highest incidence of asthma, along with heightened rates of asthma-related morbidity and mortality. 

Similar to worldwide data, the mortality rate of asthma in the United States has also undergone a consistent decline. The current mortality rate is 9.86 per million compared to 15.09 per million in 2001. However, mortality rates remain consistently higher for Black patients compared to their White counterparts. According to the CDC, from 1999 to 2016, asthma death rates among adults aged 55 to 64 were 16.32 per 1 million persons, 9.95 per 1 million for females, 9.39 per 1 million for individuals who were not Hispanic or Latino, and notably higher at 25.60 per 1 million for Black patients.

• Pathophysiology

Asthma is a syndrome characterized by diverse underlying mechanisms and involves intricate interactions among inflammatory and resident airway cells. These mechanisms lead to airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness (see Image.  Pathophysiology of Asthma). 

Airway Inflammation

The activation of mast cells by cytokines and other mediators plays a pivotal role in the development of clinical asthma. Following initial allergen inhalation, affected patients produce specific IgE antibodies due to an overexpression of the T-helper 2 subset (Th2) of lymphocytes relative to the Th1 type. Cytokines produced by Th2 lymphocytes include IL-4, IL-5, and IL-13, which promote IgE and eosinophilic responses in atopy. Once produced, these specific IgE antibodies bind to receptors on mast cells and basophils. Upon additional allergen inhalation, allergen-specific IgE antibodies on the mast cell surface undergo cross-linking, leading to rapid degranulation and the release of histamine, prostaglandin D2 (PGD2), and cysteinyl leukotrienes C4 (LTC4), D4 (LTD4), and E4 (LTE4). [23] [24] This triggers contraction of the airway smooth muscle within minutes and may stimulate reflex neural pathways. Subsequently, an influx of inflammatory cells, including monocytes, dendritic cells, neutrophils, T lymphocytes, eosinophils, and basophils, may lead to delayed bronchoconstriction several hours later. 

Airflow Obstruction

The narrowing of the airway lumen throughout the tracheobronchial tree is caused by the contraction of airway smooth muscle, thickening of the airway wall due to edema, mucus plugging in the airways, and airway remodeling, which collectively contributes to varying levels of airflow obstruction.

Mediators such as histamine and leukotrienes, released from inflammatory cells or through reflex neural pathways, trigger the contraction and relaxation of airway smooth muscle. The precise mechanism leading to airway hyperresponsiveness, characterized by an excessive tightening of the airway's smooth muscles in response to various physical, chemical, or environmental triggers, remains unclear. Some researchers propose alterations in breathing patterns where smooth muscles contract excessively or fail to relax adequately during deep breaths as a potential explanation.

Airway remodeling, which involves thickening of the basement membrane, deposition of collagen, and shedding of epithelial cells, can lead to irreversible changes in the airways. This process accelerates the decline in lung function, particularly in individuals with severe and early-onset asthma. [25]  In addition, remodeling contributes to the heightened bronchial sensitivity observed in asthma.

Arachidonic acid metabolism by the enzyme 5-lipoxygenase (5-LO) leads to the generation of leukotrienes, which serve as potent bronchoconstrictors. The metabolism of arachidonic acid by the 2 cyclooxygenase (COX) isoforms—COX-1 and COX-2—generates prostaglandins and thromboxanes. PGD2 is a potent bronchodilator, while PGE2 suppresses the production of leukotrienes. Patients with AERD have dysregulated arachidonic acid metabolism, causing decreased production of PGE2 and loss of control of leukotriene production. [26]

Patients with occupational-induced asthma can undergo an immunologically mediated response similar to those without occupational-induced asthma. Alternatively, others may present with nonimmunological occupational asthma. The possible underlying mechanisms of the nonimmunological form are denudation of the airway epithelium, direct β-2 adrenergic receptor inhibition, or elaboration of substance P by injured sensory nerves.

• History and Physical

The 4 cardinal symptoms associated with asthma are wheezing, cough (often worse at night), shortness of breath, and chest tightness. Individuals may experience 1 or more of these symptoms. Asthma symptoms typically occur intermittently, lasting for hours to days, and resolve upon the removal of triggers or the administration of asthma medications. Nighttime exacerbation of symptoms or onset triggered by exercise, cold air, or allergen exposure suggests asthma. In contrast to exertional dyspnea, which manifests shortly after beginning exertion and resolves within 5 minutes of cessation, exercise-induced asthma symptoms typically emerge around 15 minutes into activity and dissipate within 30 to 60 minutes afterward. Patients may also have a history of other forms of atopy, such as eczema and hay fever.

During patient history-taking, healthcare professionals should inquire about particular triggers that exacerbate symptoms. Common household triggers include dust, animals, and infestations of rodents and cockroaches. Some individuals may experience intermittent asthma symptoms related to their work shifts. A strong family history of asthma and allergies, or a personal history of atopic conditions and childhood asthma symptoms, suggests asthma in patients exhibiting suggestive symptoms.

Physical Examination

During physical examination, widespread, high-pitched wheezes are a characteristic finding associated with asthma. However, wheezing is not specific to asthma and is typically absent between acute exacerbations. Findings suggestive of a severe asthma exacerbation include tachypnea, tachycardia, a prolonged expiratory phase, reduced air movement, difficulty speaking in complete sentences or phrases, discomfort when lying supine due to breathlessness, and adopting a "tripod position." [27]  The use of the accessory muscles of breathing during inspiration and pulsus paradoxus are additional indicators of a severe asthma attack.

Healthcare professionals may identify extrapulmonary findings that support the diagnosis of asthma, such as pale, boggy nasal mucous membranes, posterior pharyngeal cobblestoning, nasal polyps, and atopic dermatitis. Nasal polyps should prompt further inquiry about anosmia, chronic sinusitis, and aspirin sensitivity to evaluate for AERD. Although AERD is uncommon in children or adolescents, the presence of nasal polyps in a child with lower respiratory disease should prompt an evaluation for cystic fibrosis. Clubbing, characterized by bulbous fusiform enlargement of the distal portion of a digit, is not associated with asthma and should prompt evaluation for alternative diagnoses. Please see StatPearls' companion resource, " Nail Clubbing ," for further information.

Intermittent symptoms consistent with asthma, in addition to wheezing observed during physical examination, strongly indicate asthma. Confirming the diagnosis involves the exclusion of alternative diagnoses and a demonstration of variable airflow limitation, usually seen in spirometry. 

Spirometry assesses forced expiratory volume in 1 second (FEV 1 ) and forced vital capacity (FVC) by measuring a maximal inhalation followed by rapid and forceful exhalation into a spirometer. Asthma typically presents as an obstructive pattern on spirometry, indicated by a reduced FEV 1 to FVC ratio. [28] Additionally, a visual examination of the expiratory flow-volume loop can reveal an obstructive pattern. A scooped, concave appearance in the expiratory portion of the flow-volume loop indicates diffuse intrathoracic airflow obstruction characterizes asthma. In rare cases where complete exhalation is impossible, the FEV 1 /FVC ratio may appear normal, falsely suggesting a restrictive pattern if not assessed along with flow-time curves.

Patients showing airflow limitations on spirometry receive 2 to 4 puffs of a short-acting bronchodilator like albuterol, followed by repeat spirometry in 10 to 15 minutes. According to the European Respiratory Society/American Thoracic Society guidelines, a positive BDR is determined by a change in FEV 1 or FVC compared to their predicted value. Clinicians calculate the patient's BDR using the formula:

BDR=([Post-bronchodilator value – Pre-bronchodilator value] × 100) / Predicted value of either FEV 1 or FVC

Increases exceeding 10% are considered significant. [28]  

According to the Global Initiative for Asthma, a significant BDR is indicated by an increase in the FEV 1  of 12% or 200 mL or more. In addition, the slow vital capacity, or the maximal amount of air exhaled in a relaxed expiration from full inspiration to residual volume over 15 seconds, may also be helpful when the FVC is reduced and airway obstruction is present. During slow exhalation, airway narrowing is less pronounced, and the patient can produce a larger vital capacity. In cases of restrictive disease, both slow and fast exhalations result in reduced vital capacity.

Spirometry results may be normal in asymptomatic individuals or those with cough-variant asthma. Bronchodilator responsiveness is evident in asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis, non-cystic fibrosis bronchiectasis, and bronchiolitis. However, patients with asthma may yield false negative results if they are on chronic controller medications, exhibit underlying airway remodeling, have minimal symptoms during testing, or have recently used bronchodilators before the test. Ideally, clinicians should conduct baseline spirometry before commencing treatment. [29] [30]

Bronchoprovocation Testing

During bronchoprovocation testing, clinicians induce bronchoconstriction using inhaled methacholine or mannitol, exercise, or eucapnic hyperventilation of dry air. This testing method can be beneficial for patients presenting with atypical symptoms or an isolated cough. Patients receive incremental doses of the provocative agent followed by spirometry to generate a dose-response curve. A fall in FEV 1  of 20% or more from baseline with the standard dose of methacholine or a decline of 15% or more with the standard dose of hypertonic saline, mannitol, or hyperventilation indicates a positive test. [31]  Clinicians may also conduct additional provocative testing using exercise, aspirin, and exposure to environmental triggers encountered in the workplace.

Peak Flow Meter

Although consistent reductions of 20% during symptomatic periods, followed by a gradual return to baseline as symptoms resolve, indicate asthma, clinicians typically use peak flow measurement to monitor patients with known asthma rather than for initial diagnosis. To measure peak flow, the patient takes a maximal breath and seals the peak flow meter between their lips before blowing forcefully for 1 to 2 seconds. Please see StatPearls' companion resource, " Peak Flow Measurement ," for additional information regarding peak flow measurement and its clinical significance in the evaluation and management of asthma.

Patients repeat this process 3 times, recording the highest reading as the current peak flow measurement. Patients can compare their recorded values to established graphs based on age and height for adults and height for adolescents to determine their predicted value. Notably, reduced peak flow values are not specific to asthma. Patients with either an obstructive or restrictive pattern on spirometry can have decreased peak flow values. Additionally, the accuracy of results is highly contingent on patient effort. 

Exhaled Nitric Oxide

Eosinophilic airway inflammation causes an upregulation of nitric oxide synthase in the respiratory mucosa,  leading to elevated nitric oxide levels in exhaled breath. In certain asthma patients, the fractional exhaled nitric oxide (FE NO ) surpasses levels observed in individuals without asthma. A FE NO of measurement exceeding 40 to 50 ppb can aid in confirming an asthma diagnosis. 

Pulse Oximetry

Pulse oximetry can help assess the severity of an asthma attack or monitor for deterioration. Notably, pulse oximetry measurements may exhibit a lag, and the physiological reserve of many patients implies that a declining oxygen level on pulse oximetry is a late stage, indicating an increasingly unwell or peri-arrest patient.

No specific laboratory tests are necessary for diagnosing asthma. However, patients who present with a severe asthma exacerbation should undergo a complete blood count to evaluate eosinophil levels and check for anemia, which may be the underlying cause of the patient's dyspnea. A significantly elevated eosinophil count should prompt further investigation for conditions, including parasitic infections such as Strongyloides , drug reactions, and syndromes characterized by pulmonary infiltrates with eosinophilia. These syndromes include allergic bronchopulmonary aspergillosis, eosinophilic granulomatosis with polyangiitis, and hypereosinophilic syndrome (see Image.  Allergic Bronchopulmonary Aspergillosis on CT Scan). 

Non-smoking patients who present with irreversible airflow obstruction should undergo serum α1-antitrypsin level testing to rule out emphysema caused by homozygous α1-antitrypsin deficiency. Allergy testing may prove beneficial for patients experiencing symptoms upon exposure to specific allergens. Clinicians should obtain total serum IgE levels in patients with moderate-to-severe persistent asthma, particularly when considering treatment with anti-IgE monoclonal antibodies or when there is suspicion of allergic bronchopulmonary aspergillosis. Please refer to the Treatment/Management  section for further details on anti-IgE monoclonal antibodies.

Chest radiographs in asthma patients are often normal; however, during acute exacerbations, abnormal findings such as hyperinflation, pneumomediastinum, and bronchial thickening may be observed (see Image.  A Chest Radiograph Depicting Asthma). A chest radiograph is recommended for patients aged 40 or older with new-onset, moderate-to-severe asthma to rule out conditions that can mimic asthma, such as a mediastinal mass with tracheal compression or heart failure.

Additional indications for chest radiography include patients experiencing symptoms that are difficult to control, fever, chronic purulent sputum production, persistently localized wheezing, hemoptysis, weight loss, clubbing, inspiratory crackles, significant hypoxemia, and moderate or severe airflow obstruction that does not reverse with bronchodilators. High-resolution computed tomography is necessary to clarify any abnormalities noted on chest radiographs or for patients with other suspected conditions that may not be well visualized on routine radiographs.

Evaluation During an Acute Exacerbation

Each patient should undergo a rapid assessment of their vital signs, including oxygen saturation. Measuring the peak flow can indicate the severity of the exacerbation and monitor the response to therapy. Predicted peak flow measurements vary based on age and height; however, a peak flow below 200 L/min indicates severe obstruction except in patients aged 65 or older or with very short stature. A peak flow measurement below 50% predicted or the patient's personal best is considered severe, while between 50% and 70% is considered moderate. Chest radiographs are not uniformly necessary unless the diagnosis of acute asthma exacerbation is uncertain, the patient requires hospitalization, or evidence of a comorbid condition is present.

Identification of Patients at Risk of Fatal or Near-Fatal Asthma

Most asthma-related deaths are preventable if risk factors are identified and addressed early. Major risk factors that place patients at high risk for future fatal asthma exacerbations include:

• A recent history of poorly controlled asthma
• A prior history of near-fatal asthma
• A history of endotracheal intubation for asthma 
• A history of intensive care unit admission for asthma

Minor risk factors include exposure to aeroallergens and tobacco smoke, illicit drug use, older patients, aspirin sensitivity, long duration of asthma, and frequent hospitalizations for asthma-related issues.

• Treatment / Management

Patient Education

Multiple sources of patient education are available. According to the National Asthma Education and Prevention Program's Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, personalized education from the patient's primary clinician is especially impactful. Studies reveal that such education reduces the number of asthma exacerbations and hospitalizations. Healthcare professionals should provide culturally specific asthma education that includes understanding asthma and its symptoms, identifying the patient's specific triggers, and strategies for their avoidance. Each patient should understand how to properly use an inhaler and be familiar with medications that serve as rescue options, those used for symptom control, and those that may fulfill both roles. Clinicians should inquire about any obstacles hindering medication adherence and work collaboratively with patients to overcome concerns or barriers, thus enhancing overall adherence.

Although the data on effectiveness are limited, a general consensus among experts exists that individuals with asthma should possess a personalized "action plan" to follow at home (please refer to the link to an action plan download in the  Deterrence and Patient Education section). This action plan provides a structured maintenance medication regimen and delineates steps to take when symptoms exacerbate. Clinicians develop an action plan based on symptoms or peak flow readings and divide it into 3 zones—green, yellow, and red. 

Patients in the green zone are asymptomatic, with peak flows at 80% or higher than their personal best. They feel well and continue with their long-term control medication. Peak flow readings falling within the yellow zone range between 50% and 79% of the patient's personal best, accompanied by symptoms such as coughing, wheezing, and shortness of breath, which begin to interfere with activity levels. In the red zone, patients experience peak flow readings below 50% of their best, severe shortness of breath, and an inability to perform everyday activities.

Asthma Severity

Guidelines established by the National Asthma Education and Prevention Program (NAEPP) and the Global Initiative for Asthma (GINA) determine therapy based on the frequency and severity of asthma symptoms, the degree of respiratory impairment, and the risk of future exacerbations. Risk factors contributing to future exacerbations include frequent asthma symptoms, a history of intensive care unit admission for asthma, obesity, poor medication adherence, chronic rhinosinusitis, and a low FEV 1 . The severity categories and treatment guidelines vary based on age. This activity will address asthma severity and management in adolescents and adults aged 12 or older. Please see StatPearls' companion resource, " Pediatric Asthma ," for additional information regarding the treatment of asthma in infants and children. 

Every patient should have access to a bronchodilator with a rapid onset of action. Traditionally, this has been a short-acting β-agonist (SABA) such as albuterol. However, GINA recommends a low-dose glucocorticoid/formoterol inhaler, such as 80 to 160 mcg budesonide/4.5 mcg formoterol inhaled by mouth 1 or 2 times daily,  for asthma symptoms. Notably, this is an off-label indication for this preparation.

Treatment progresses in a stepwise manner, with the highest severity category in which the patient experiences any symptoms, designating the treatment category from which the patient receives treatment (see Image.  Asthma Severity Classification by National Asthma Education and Prevention Program). Tables 1 and 2 below include the NAEPP and GINA asthma severity classifications and treatment initiation guidelines based on the patient's symptoms and lung function.

Table 1. National Asthma Education and Prevention Program: Expert Panel Working Group Initial Asthma Therapy in Adolescents and Adults.

Abbreviations: FEV 1 , forced expiratory volume in 1 second; ICS, inhaled corticosteroid; LABA, long-acting β-agonist; LAMA, long-acting muscarinic antagonist; LTRA, leukotriene receptor antagonist; SABA, short-acting β-agonist.

Table 2. Global Initiative for Asthma Initial Asthma Therapy in Adolescents and Adults.

Abbreviations: ICS, inhaled corticosteroid; LABA, long-acting β-agonist; LAMA, long-acting muscarinic antagonist; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroid; SABA, short-acting β-agonist.

Routine follow-up every 1 to 6 months is necessary to ensure adequate symptom management. Upon reevaluation, patients facing inadequate asthma symptom management, exacerbations necessitating systemic glucocorticoids, or those at high risk of exacerbation on their current therapy level should escalate to the next level of therapy. Therapy adjustments proceed incrementally until symptoms are adequately managed. After maintaining control for 3 to 6 months, clinicians may consider gradual therapy reduction following the stepwise protocols outlined by GINA or NAEPP guidelines.

Severe Asthma

Adults and adolescents with severe asthma that remains uncontrolled despite Step 4 recommended therapy should receive a LAMA, such as tiotropium, alongside their inhaled glucocorticoid and LABA regimen. Clinicians should direct these patients for phenotypic assessment and consideration for biological therapy options. Anti-IgE monoclonal antibody therapy with omalizumab may be helpful for those still experiencing inadequate control and possessing documented sensitivity to a perennial allergy with IgE levels ranging between 30 and 700 IU/mL.

Patients with severe eosinophilic asthma who are not adequately controlled can utilize mepolizumab and reslizumab, monoclonal antibodies against IL-5, benralizumab, a monoclonal antibody against the IL-5 receptor α-subunit, and dupilumab a monoclonal antibody against the IL-4 receptor α-subunit. Tezepelumab is a human monoclonal IgG2-λ antibody that binds to TSLP, preventing its interaction with the TSLP receptor complex. [32]

Acute Exacerbation

Patients experiencing an acute asthma exacerbation may manage symptoms at home or need urgent medical care depending on their symptom severity and risk factors for fatal asthma. These risk factors include prior life-threatening exacerbations, exacerbations despite glucocorticoid use, more than 1 asthma-related hospitalization or 3 emergency room visits in the past year, and comorbidities such as cardiovascular or chronic lung disease. Immediate medical attention is warranted for patients showing significant breathlessness, inability to speak beyond short phrases, reliance on accessory muscles, or peak flow measurements at 50% or less of their baseline measurement.

All patients require a fast-acting β-agonist. Potential options include the LABA formoterol combined with ICS, the SABA albuterol combined with budesonide, or albuterol alone. Combination with ICS is the preferred choice. Albuterol dosing is 2 to 4 puffs from a metered dose inhaler (MDI) at home and 4 to 8 puffs in the office with a valved holding chamber or spacer every 20 minutes for 1 hour as needed. Albuterol may also be nebulized. ICS-formoterol dosing is 1 to 2 puffs every 20 minutes for 1 hour as required, with a maximum of 8 puffs per day. 

Patients whose symptoms improve after administering a bronchodilator and whose peak flow returns to 80% of their baseline or better can continue to manage their symptoms at home. Oral glucocorticoids equivalent to 40 to 60 mg prednisone daily for 5 to 7 days are warranted for the following patients:

• Those experiencing recurrent symptoms over the following 1 to 2 days.
• Those whose peak flow remains less than 80% of their normal baseline (high-dose ICSs are an alternative).
• If they do not improve after 1 to 3 doses of a fast-acting bronchodilator.
• If they have recently completed a course in OCS.
• Those who are on a maximal dose of controller medications.

Patients with a peak flow value of 50% or lower despite administering a bronchodilator or continuing to worsen should seek immediate medical care while continuing to administer their fast-acting bronchodilator. 

Office management is similar to home management, with the addition that according to GINA guidelines, all patients with oxygen saturation below 90% should receive oxygen to maintain saturation above 92% or 95% for pregnant individuals. Albuterol treatment can be administered via an MDI or nebulizer, with a dosage of 4 to 8 puffs or 2.5 to 5 mg every 20 minutes for 1 hour, respectively. Research comparing the efficacy of an MDI combined with a valved-holding chamber to nebulizer delivery, both administering the same β-agonist but with significantly lower doses via MDI, demonstrates similar enhancements in lung function and risk reduction for hospitalization. [33] [34] [35]  

If oral glucocorticoids are unavailable, intramuscular steroids such as triamcinolone suspension (40 mg/mL) 60 to 100 mg can be an alternative. However, it is noteworthy that intramuscular glucocorticoids have a delayed onset of action of 12 to 36 hours. Patients meeting certain criteria such as a respiratory rate of 30 breaths per minute, a heart rate of more than 120 bpm, a continued peak flow of less than 50% predicted, oxygen saturation of less than 90%, or the inability to speak in full sentences should be transferred to the emergency department. 

Patients who can be sent home from the office should have their controller medications advanced in 1 step. In addition, it is essential to review the correct use of their inhaler, discuss trigger avoidance strategies, ensure they have an asthma action plan, and emphasize the importance of adhering to their controller medication.

Emergency Department Care

Within the first hour, patients should receive 3 treatments of an inhaled SABA, such as albuterol, via a nebulizer or MDI, followed by repeat dosing every 1 to 4 hours. In addition to a SABA, patients with severe asthma exacerbations should also receive inhaled ipratropium, a short-acting muscarinic antagonist (SAMA), at a dosage of 500 µg by nebulization or 4 to 8 puffs by MDI, every 20 minutes for 3 doses, and then hourly as needed for up to 3 hours. Current guidelines recommend discontinuing SAMA therapy once the patient requires hospital admission, except in specific cases such as refractory asthma requiring treatment in the intensive care unit, concurrent treatment with monoamine oxidase inhibitors due to potential increased toxicity from sympathomimetic therapy due to impaired drug metabolism, presence of COPD with an asthmatic component, or asthma triggered by β-blocker therapy.

As with outpatient management, patients also receive glucocorticoids equivalent to 40 to 60 mg of prednisone daily for 5 to 7 days. A systematic review reveals no difference between a higher dose and a longer course when compared to a lower dose with a shorter course of prednisone or prednisolone. [36]  Oral and intravenous glucocorticoids have equivalent effects when administered in comparable doses. Intravenous steroids are necessary for patients with impending or actual respiratory arrest or who are intolerant of oral glucocorticoids. Some clinicians administer higher doses of glucocorticoids for severe asthma exacerbations based on their expert opinion and concern that a lower dose might be insufficient in a critically ill patient. 

Magnesium sulfate

Per GINA guidelines, magnesium is not recommended for routine use in asthma exacerbations. However, a 1-time dose of 2 g given intravenously over 20 minutes reduces hospitalization rates in adults with an FEV 1  less than 25% to 30% predicted on presentation and in those who fail to respond to initial treatment and continue to have hypoxemia. Nebulized MgSO 4  is not beneficial in the management of an acute asthma exacerbation.

A Cochrane Database review in 2014 concluded that a single infusion of intravenous MgSO 4 for patients not responding to conventional therapy results in improved lung functions and fewer hospital admissions. [37]  However, in a recent systematic review, the comparison of the same studies, eliminating those involving children and those containing only abstracts, revealed conflicting results. The review examined the effects of intravenous and nebulized MgSO 4 . Although 3 out of 9 studies addressing treatment with intravenous MgSO 4 found a significant effect on lung function compared to placebo, these results are not statistically significant. [38]  Only 2 of the 8 studies investigating hospital admission rates reveal a significant effect of MgSO 4 . [38]  Conversely, 6 of the 9 studies investigating treatment with nebulized MgSO 4 compared to placebo reveal a favorable effect on the FEV 1  and peak expiratory flow rate. [38]  These results somewhat contradict the Cochrane Database review conducted in 2014, which evaluated the same studies. [37]  

An additional study reveals a small benefit of adding inhaled magnesium to inhaled albuterol plus ipratropium in reducing hospital admissions but no significant improvement in peak expiratory flow when added to inhaled albuterol plus ipratropium or inhaled albuterol alone. [39]  

Intubation or Noninvasive Ventilation

Indications for intubation and mechanical ventilation or noninvasive ventilation include the following:

• Slowing of the respiratory rate
• Depressed mental status
• Inability to maintain respiratory effort
• Inability to cooperate with the administration of inhaled medications
• Worsening hypercapnia and associated respiratory acidosis
• Inability to maintain oxygen saturation above 92% despite face mask supplemental oxygen

A 1- to 2-hour trial of bilevel noninvasive positive pressure ventilation is appropriate for patients with an acute asthma exacerbation, but clinicians should maintain a low threshold for intubation. [40] [41]  

Additional Therapies

Occasionally, nonstandard therapies, such as ketamine, halothane, helium-oxygen mixtures, extracorporeal membrane oxygenation, and parenteral terbutaline, can be helpful for certain patients. However, these therapies are not routinely utilized due to limited evidence of efficacy. The indication for parenteral epinephrine is asthma associated with anaphylaxis and angioedema.

All patients who are smokers should be educated on the benefits of smoking cessation and provided with appropriate support and resources. Empiric antibiotics are not recommended since most infections triggering asthma exacerbations are viral. According to both GINA and NAEPP guidelines, intravenous methylxanthines such as theophylline are deemed ineffective and are no longer part of the standard of care. [42]

• Differential Diagnosis

The differential diagnoses for asthma include the following conditions:

• Bronchiectasis
• Bronchiolitis
• Chronic obstructive pulmonary disease
• Chronic sinusitis
• Cystic fibrosis
• α1-antitrypsin deficiency
• Aspergillosis
• Exercise-induced anaphylaxis
• Foreign body aspiration
• Heart failure
• Gastroesophageal reflux disease
• Tracheomalacia
• Pulmonary embolism
• Pulmonary eosinophilia
• Sarcoidosis
• Upper respiratory tract infection
• Vocal cord dysfunction
• Eosinophilic granulomatosis with polyangiitis
• Bronchogenic carcinoma
• Post-viral tussive syndrome
• Eosinophilic bronchitis
• Cough induced by angiotensin-converting enzyme inhibitors
• Bordetella pertussis infection
• Interstitial lung disease
• Recurrent oropharyngeal aspiration

The development and prognosis of asthma involve a complex interplay of genetic and environmental factors. Social determinants of health, such as poor housing quality and indoor and outdoor pollution, profoundly impact asthma prognosis. In the United States, asthma is a chronic illness characterized by a significant racial and ethnic disparity in both prevalence and prognosis. Underrepresented racial and ethnic minorities, as well as individuals living below the poverty line, experience higher morbidity rates, increased emergency room visits, hospitalizations, and mortality due to asthma. [43] [44]  Additionally, lack of access to healthcare—whether due to difficulties in accessing clinicians or lack of insurance—further exacerbates prognosis-related challenges.

The international asthma mortality rate reaches as high as 0.86 deaths per 100,000 persons in certain countries. The overall prognosis is predominantly linked to lung function, with mortality rates 8 times higher among individuals in the bottom 25% of lung function. Several factors contribute to a poorer prognosis, including inadequate asthma management, age 40 or older, a history of more than 20 pack-years of cigarette smoking, blood eosinophilia, and FEV1 of 40% to 69% of predicted values

• Complications

The complications related to asthma include disease-related complications and adverse effects of glucocorticoids, LTRA, and endotracheal intubation. The following list contains complications associated with asthma:

• Decline in lung function
• Osteoporosis
• Adrenal suppression
• Hypertension
• Peptic ulcer
• Sleep disorders
• Obstructive sleep apnea
• Mood disorders
• Cardiac arrest
• Respiratory failure or arrest  
• Pneumothorax
• Aspiration [45]
• Consultations

Healthcare professionals should seek consultation with an asthma specialist in pulmonology or allergy when the diagnosis of asthma is uncertain, the patient's symptoms remain poorly controlled, medication adverse effects become intolerable, or the patient experiences frequent exacerbations. Accessing appropriate specialist care aids in excluding alternate diagnoses, determining the need for additional diagnostic testing, and effectively escalating medical therapy.

• Deterrence and Patient Education

Patient education plays a pivotal role in the effective management of asthma by clinicians. To deter exacerbations and improve patient outcomes, clinicians should emphasize the importance of adherence to medication regimens, avoidance of triggers, and regular monitoring of symptoms. Educating patients about asthma triggers, such as allergens, air pollution, and tobacco smoke, can empower them to make informed lifestyle choices. Furthermore, clinicians should highlight the significance of having an asthma action plan, which outlines steps to take during worsening symptoms or exacerbations. See the National Heart and Lung Institute's website, " Asthma Action Plan ," for a printable version of an action plan.

Patient education should also prioritize the recognition of early warning signs of an asthma attack and prompt seeking of medical attention when necessary. Routine follow-up visits for patients with active asthma are recommended, occurring every one to six months, contingent on the severity of asthma and adequacy of control. During these follow-up visits, clinicians should assess asthma control, lung function, exacerbations, inhaler technique, adherence, adverse effects of medication, quality of life, and patient satisfaction with care. By instilling a comprehensive understanding of asthma management strategies and fostering proactive patient involvement, clinicians can significantly reduce the burden of asthma and enhance patient well-being.

• Enhancing Healthcare Team Outcomes

Asthma is characterized by complex pathophysiology involving airway inflammation, intermittent airflow obstruction, and bronchial hyperresponsiveness. The condition presents various signs and symptoms, such as wheezing, coughing, shortness of breath, and chest tightness. Wheezing may not always be present, particularly in cases primarily affecting small airways, and its absence does not exclude asthma. Additionally, a cough might be the sole symptom, especially one that occurs or worsens at night. Diagnostic evaluation involves spirometry, assessing lung function parameters such as FEV1 and FVC, measuring peak flow, and possibly conducting bronchoprovocation testing in some individuals.

Treatment strategies include trigger avoidance, ensuring access to rescue medications, and personalized pharmacological interventions, with inhaled corticosteroids being the preferred controller medication. Patient education, regular assessment of symptom control, and adherence to treatment plans are crucial components in effectively managing asthma. Adequate patient readiness and preparation, including the development of an asthma action plan, help minimize illness severity and optimize patient outcomes by promoting self-management and reducing healthcare utilization.

Enhancing patient-centered care, outcomes, patient safety, and team performance in asthma management demands a strategic approach. Each healthcare team member should possess the necessary clinical expertise to diagnose and treat asthma effectively, which involves interpreting spirometry findings and customizing treatment plans according to individual patient needs. Adhering to evidence-based guidelines and protocols will ensure uniform practices across healthcare settings. 

Effective interprofessional communication enables the exchange of information, collaborative decision-making, and seamless care transitions. Each healthcare team member, including physicians, advanced care practitioners, nurses, pharmacists, respiratory therapists, and social workers, contributes unique skills to asthma care, further enriching interdisciplinary collaboration. By fostering a culture of collaboration, communication, and coordination, healthcare professionals can deliver comprehensive, patient-centered asthma care, decreasing morbidity and mortality and enhancing team performance.

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Pathophysiology of Asthma. Figure A displays the location of the lungs and airways in the body. Figure B shows a cross section of a normal airway. Figure C illustrates a cross section of an airway during asthma symptoms National Institutes of Health

A Chest Radiograph Depicting Asthma. The image depicts both anterior and lateral radiographs of a patient with asthma. The image highlights the presence of pneumomediastinum and increased bronchovascular markings. Contributed by H Shulman, MD

Allergic Bronchopulmonary Aspergillosis on CT Scan. Computed tomography (CT) images reveal bronchiectasis in both upper lobes of a patient with bronchial asthma, indicative of allergic bronchopulmonary aspergillosis. Contributed by M Salahuddin, MD

Asthma Severity Classification by The National Asthma Education and Prevention Program. Contributed by R Chabra, DO

Disclosure: Muhammad Hashmi declares no relevant financial relationships with ineligible companies.

Disclosure: Mary Cataletto declares no relevant financial relationships with ineligible companies.

This book is distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ( http://creativecommons.org/licenses/by-nc-nd/4.0/ ), which permits others to distribute the work, provided that the article is not altered or used commercially. You are not required to obtain permission to distribute this article, provided that you credit the author and journal.

• Cite this Page Hashmi MF, Cataletto ME. Asthma. [Updated 2024 May 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.

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Advances and recent developments in asthma in 2020

Affiliations.

• 1 Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Davos, Switzerland.
• 2 Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
• 3 Department of Medical Immunology, Institute of Health Sciences, Bursa Uludag University, Bursa, Turkey.
• 4 Faculty of Medicine, Division of Pediatric Allergy and Immunology, Marmara University, Istanbul, Turkey.
• 5 Department of Allergology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
• 6 Swiss Institute for Bioinformatics (SIB), Davos, Switzerland.
• 7 Department of Otolaryngology Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing, China.
• 8 Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
• 9 Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
• 10 Faculty of Medicine, Transylvania University, Brasov, Romania.
• PMID: 32997808
• DOI: 10.1111/all.14607

In this review, we discuss recent publications on asthma and review the studies that have reported on the different aspects of the prevalence, risk factors and prevention, mechanisms, diagnosis, and treatment of asthma. Many risk and protective factors and molecular mechanisms are involved in the development of asthma. Emerging concepts and challenges in implementing the exposome paradigm and its application in allergic diseases and asthma are reviewed, including genetic and epigenetic factors, microbial dysbiosis, and environmental exposure, particularly to indoor and outdoor substances. The most relevant experimental studies further advancing the understanding of molecular and immune mechanisms with potential new targets for the development of therapeutics are discussed. A reliable diagnosis of asthma, disease endotyping, and monitoring its severity are of great importance in the management of asthma. Correct evaluation and management of asthma comorbidity/multimorbidity, including interaction with asthma phenotypes and its value for the precision medicine approach and validation of predictive biomarkers, are further detailed. Novel approaches and strategies in asthma treatment linked to mechanisms and endotypes of asthma, particularly biologicals, are critically appraised. Finally, due to the recent pandemics and its impact on patient management, we discuss the challenges, relationships, and molecular mechanisms between asthma, allergies, SARS-CoV-2, and COVID-19.

Keywords: COVID-19; asthma biomarkers; asthma phenotypes; biological therapeutics; comorbidities.

© 2020 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Publication types

• Asthma / diagnosis
• Asthma / epidemiology*
• Asthma / therapy
• Comorbidity
• Hypersensitivity / diagnosis
• Hypersensitivity / epidemiology*
• Hypersensitivity / therapy
• Precision Medicine
• Risk Factors