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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 ].

figure 1

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.

figure 2

(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 ].

figure 3

(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 ].

figure 4

(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 ].

figure 5

(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 ].

figure 6

(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.

figure 7

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.

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Giorgio Walter Canonica

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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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A systematic review of psychological, physical health factors, and quality of life in adult asthma

  • Sabina Stanescu   ORCID: orcid.org/0000-0003-0792-8939 1 ,
  • Sarah E. Kirby 1 , 2 ,
  • Mike Thomas   ORCID: orcid.org/0000-0001-5939-1155 2 , 3 ,
  • Lucy Yardley 1 &
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npj Primary Care Respiratory Medicine volume  29 , Article number:  37 ( 2019 ) Cite this article

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  • Outcomes research
  • Quality of life

Asthma is a common non-communicable disease, often characterized by activity limitation, negative effects on social life and relationships, problems with finding and keeping employment, and poor quality of life. The objective of the present study was to conduct a systematic review of the literature investigating the potential factors impacting quality of life (QoL) in asthma. Electronic searches were carried out on: MEDLINE, EMBASE, PsycINFO, the Cochrane Library, and Web of Science (initial search April 2017 and updated in January 2019). All primary research studies including asthma, psychological or physical health factors, and quality of life were included. Narrative synthesis was used to develop themes among findings in included studies in an attempt to identify variables impacting QoL in asthma. The search retrieved 43 eligible studies that were grouped in three themes: psychological factors (including anxiety and depression, other mental health conditions, illness representations, and emotion regulation), physical health factors (including BMI and chronic physical conditions), and multifactorial aspects, including the interplay of health and psychological factors and asthma. These were found to have a substantial impact on QoL in asthma, both directly and indirectly, by affecting self-management, activity levels and other outcomes. Findings suggest a complex and negative effect of health and psychological factors on QoL in asthma. The experience of living with asthma is multifaceted, and future research and intervention development studies should take this into account, as well as the variety of variables interacting and affecting the person.

Introduction

Over 235 million people worldwide are living with asthma, which is one of the leading non-communicable diseases worldwide. 1 , 2 Symptoms, exacerbations, and triggers in asthma are associated with lower quality of life (QoL), tiredness, activity limitation, negative effects on social life and relationships, problems with finding and keeping employment, and reduced productivity. 3 , 4 , 5 , 6 , 7 People with asthma are up to six times more likely than the general population to have anxiety or depression, 8 and 16% of people with asthma in the UK have panic disorder, 9 compared to 1% in the general population. 10 People with brittle asthma (difficult-to-control asthma with severe, recurrent attacks) demonstrate even greater comorbidity and maladaptive coping styles. 11 Psychological dysfunction is often unrecognized in primary care, despite being significantly associated with poor asthma outcomes, including asthma control and QoL. 8 , 12 , 13 Indeed, the European Asthma Research and Innovation Partnership has identified understanding the role of psychological factors as an unmet need in improving asthma outcomes. 14 , 15 They propose that anxiety and depression are present at all three stages of the experience of asthma: onset, progression, and exacerbation. 14

A recent meta-analysis found that asthma diagnoses significantly increased the risk of psychological and health conditions (such as cardiovascular/cerebrovascular diseases, obesity, hypertension, diabetes, psychiatric and neurological comorbidities, gut and urinary conditions, cancer, and respiratory problems other than asthma). 16 In addition, studies have pointed towards an impact on QoL in people with asthma of additional health and psychological factors, such as comorbid anxiety or depression, higher body mass index(BMI), professional status, and feelings of lack of control over health (for example, refs 17 , 18 ). Such evidence reinforces the argument that the needs of people with asthma should be approached in conjunction with these additional factors, rather than using a single-illness approach, aiming to reduce the adversity of people’s experience. However, the extent to which psychological and physical health factors interact and impact asthma outcomes is yet to be systematically explored. This systematic review aims to provide a narrative synthesis of the literature exploring psychological and physical health factors that influence QoL in adults with asthma.

Study characteristics

The search and screening process identified 43 eligible papers, published between 2003 and 2019 (see Fig. 1 for PRISMA flowchart 19 ). The characteristics of each study are summarized below in Table 1 . Twelve studies were conducted in Europe, 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 17 in North America, 12 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 7 in Australia, 17 , 48 , 49 , 50 , 51 , 52 , 53 4 in Asia, 54 , 55 , 56 , 57 and 3 in Africa. 58 , 59 , 60 All papers employed a quantitative approach comprising 2 longitudinal studies 31 , 44 and 41 cross-sectional studies. Only 4 studies included a control group. 21 , 28 , 29 , 31 Overall, the majority of papers had a large sample size (ranging between 40 and 39,321 participants; 30 papers included a sample size of >100). The majority of studies recruited from primary care or the general population, using self-report to confirm a diagnosis of asthma. Only a few studies recruited from secondary and tertiary asthma clinics. 12 , 27 , 36 , 41 , 44 , 48 , 60 There was a high occurrence ( n  = 14) of exclusion criteria relating to specific demographic or asthma characteristics, as well as mental health conditions and comorbidities, which restricted the study sample without a reason being given. Most studies used self-report measures, 17 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 39 , 41 , 42 , 43 , 44 , 45 , 46 , 48 , 49 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 with a small proportion using psychiatric interviews to screen for mental health conditions. 12 , 31 , 38 , 40 , 50 The majority of studies used asthma-specific QoL measures ( n  = 29), 12 , 21 , 23 , 25 , 27 , 28 , 30 , 32 , 33 , 34 , 35 , 36 , 37 , 39 , 40 , 41 , 42 , 44 , 48 , 49 , 50 , 51 , 54 , 55 , 56 , 58 , 59 , 60 , 61 17 included an health-related QoL measure ( n  = 18), 17 , 20 , 22 , 23 , 24 , 25 , 28 , 30 , 31 , 34 , 35 , 36 , 38 , 43 , 50 , 51 , 52 , 55 and 4 used general measures of QoL ( n  = 7); 26 , 35 , 45 , 46 , 47 , 57 , 62 11 papers used >1 measure of QoL. 23 , 25 , 28 , 30 , 34 , 35 , 36 , 37 , 50 , 51 , 55 The average age across included studies was 42.1 years (and 61.57% were female). Papers report prevalence rates of between 16.8% and 48.9% for depression and between 13.3% and 44.4% for anxiety, 20 , 27 , 33 , 38 , 50 , 56 , 58 , 60 with an average of 28.31% for a diagnosis of anxiety or depression. Across several studies, the prevalence of other mental health conditions was 28.31% on average (ranging between 28% and 80%). 12 , 37 , 38 , 40 , 42 Between 72% and 86.9% of people with asthma had at least one additional physical condition and between 21% and 26.3% had ≥2; 25 , 34 , 56 26.36% had, on average, at least one other physical health condition. On average, people with asthma were significantly more likely to have a BMI of >30 (and between 61% and 75.1% had a BMI >25). 26 , 45 , 59 The quality assessment identified that most studies were of a reasonable quality; however, it should be noted that some measures used could be considered inappropriate for the research aim or the population under investigation. Examples include measuring general QoL with an asthma-specific measure or administering a geriatric depression questionnaire to a young adult population.

figure 1

PRISMA statement of included and excluded papers

Narrative synthesis

Narrative synthesis generated three overarching themes: psychological factors, health factors, and multifactorial aspects (see Table 2 for themes and subtheme descriptions). Overall, patients with asthma demonstrated impaired QoL, which was further decreased by psychological factors (e.g. anxiety, depression, emotion regulation, illness perceptions), health risk factors (such as an increased BMI), and the presence of a co-existing mental health or physical condition (such as rhinitis, cardiovascular disease, diabetes, etc.). Having more than one co-existing condition or psychological factor impacted overall QoL even more substantially. Results for each of the aspects found are presented below.

Psychological factors

Within this first theme, four subthemes were generated. These comprised ‘anxiety and depression’, ‘other mental health conditions’, ‘emotional regulation’, and ‘illness representations’.

Anxiety and depression were notably the most commonly considered factors ( n  = 30). A high prevalence of people with asthma showed symptoms of or clinical diagnoses of anxiety or depression, which appeared to play a key role in understanding the relationship between asthma and QoL. Overall, having a diagnosis of anxiety or depression was associated with poorer QoL across all dimensions (e.g. activity limitation, physical or mental wellbeing, social or role functioning, etc.), as well as health perceptions. 24 , 36 , 46 , 50 , 54 In particular, one study (of undergraduate students aged 18–25 years, with childhood-onset asthma) found that anxiety was significantly associated with asthma QoL, as was the interaction between anxiety and depression, 32 while others found that generally anxiety and depression both predicted worse QoL independently (refs 12 , 29 , 33 , 38 , 42 , 44 , 56 , 60 ). One study found that the average asthma-related QoL scores for people with asthma and depression were 1.4 times lower compared to people with asthma and no depression. 33 Having current depression or anxiety was associated with worse QoL than was having a lifetime diagnosis; this was in turn was greater than having no depression or anxiety. 45 Having a history of major depression was also significantly associated with worse physical and mental functioning, compared to those with asthma and no depression. 38 There was considerable variability across variance explained, with depression found to account for between 3% 40 and 56% 30 of the variance in QoL, whereas anxiety was found to account for between 2% 40 and 68%. 21

In contrast, one study found that having either a depressive or an anxiety disorder significantly impacted asthma QoL but having both was not significantly different than only having one, 40 which is dissonant with other studies. Another study of 90 people with difficult asthma found that having anxiety or depression had no significant effect on QoL. 48 In addition, although depression was associated with poorer QoL, it did not inflate the relationship between asthma severity and QoL. 29 All other studies were significant but showed only small-to-moderate effect sizes. Having a full clinical diagnosis of anxiety or depression was not significantly worse (in terms of QoL) than having only some symptoms of anxiety and depression.

Studies also considered the impact of anxiety and depression on specific subdomains of QoL and asthma-specific QoL. Having anxiety was not associated with physical functioning, mental health or health perception, 38 or the physical component of QoL. 20 Depression, however, was associated with significantly poorer QoL on physical dimensions and activity limitation, 20 , 21 , 23 , 30 , 38 , 45 , 53 , 55 , 58 although one study found significant results only for participants with uncontrolled asthma. 22 In relation to asthma-specific QoL, depression and anxiety were significantly associated with decreased asthma-specific QoL. 17 , 21 , 23 , 27 , 28 , 32 , 33 , 36 , 37 , 40 , 50 , 54 , 55 , 58 , 61

Nine studies looked at other mental health conditions, such as panic disorder with or without agoraphobia, 24 , 38 , 44 , 57 personality disorders, 31 alexithymia, 23 somatization, 38 mood disorders, 12 , 40 , 57 schizophrenia, eating disorders, substance use disorders, 38 and general occurrence of any psychiatric disorder. 12 , 17 The results in this subtheme were mixed, but overall they suggest that the presence of an additional mental health condition is significantly associated with a decrease in QoL in patients with asthma. 12 , 17 Panic disorder was also shown to be both significantly 24 and non-significantly 57 associated with poorer mental and physical components of QoL. Alexithymia in people with asthma was not associated with poorer QoL. 23 Having asthma and a personality disorder was associated with lower general QoL, 31 as well as lower scores for physical health, vitality, pain, general health, social function, mental health, and emotional role (physical function was not significant). This association was not found for people without asthma, suggesting that it is the combination of conditions (asthma and co-existing mental health conditions) that may lead to the negative impact on QoL. 31

The emotion regulation subtheme included studies that explored the relationship between emotional states, negative affect (not related to anxiety, depression, or other mental health conditions), or coping and QoL in people with asthma. QoL in asthma was found to be influenced by affect and a predisposition to negative states, as found by four studies. 28 , 39 , 41 , 51 For instance, a model of age, gender, negative affect, and medical problems accounted for 20% of symptoms and 23% of activity limitation. 39 This was supported by findings that negative mood is associated with poor scores on both the mental and physical components of the Asthma Quality of Life Questionnaires (AQLQ), 28 as well as a positive correlation between active coping and asthma QoL. 51 Despite heterogeneity, the impaired QoL was associated with impulsive-careless coping 41 and avoidant coping. 51 Overall, the presence of psychological distress seemed to affect people with asthma more than people without asthma in terms of QoL.

Illness-related cognitions are people’s patterns of beliefs about the characteristics of their conditions, which in turn influence their appraisal of severity and can determine future behaviours. 63 A number of illness-related cognitions and perceptions significantly predicted QoL in seven studies. 26 , 34 , 37 , 42 , 43 , 51 , 60 For instance, asthma self-efficacy 42 was positively associated with QoL. However, decreased QoL was significantly predicted by a series of varied illness perceptions: subjective illness severity, uncertainty in illness, illness intrusiveness, 43 perceived disability, 60 health beliefs and attitudes, 34 perceived severity, 34 level of confidence or self-efficacy in managing asthma, 51 satisfaction with illness, 51 anxiety sensitivity for physical concerns, 39 and satisfaction with life. 37 In addition, a model of subjective and objective illness severity accounted for 24% of the variance in QoL, further supporting the effect of illness perceptions on QoL. 34

Physical health factors

Two subthemes were generated in the physical health factors theme: additional physical conditions and BMI.

Ten papers examined additional physical conditions in relation to QoL in asthma; 25 , 27 , 34 , 39 , 46 , 47 , 48 , 49 , 52 , 53 most only referred to ‘comorbidity’ or ‘medical problems’ as a measure of frequency of additional conditions. 34 , 36 , 39 Some studies looked at both general and individual co-existing conditions 25 , 48 , 52 and others counted chronic conditions but did not include them in further analyses. 33 , 36 , 56 , 59 Of the ones that did explore individual conditions, the highest impact seemed to be provoked by musculoskeletal conditions. 25 Similarly, statistically and clinically significant decreases in activity levels were also found for people with asthma and multimorbid conditions. 52 Other conditions investigated included respiratory conditions, 47 diabetes, 25 , 48 obesity, 48 hypertension, 25 , 39 gastro-oesophageal reflux disorder, 48 rhinitis, 48 , 49 vocal cord dysfunction, 48 sleep apnoea, 48 musculoskeletal disorders, 25 , 39 arthritis, 39 , 52 heart disease, 25 stroke, 39 , 52 cancer, 39 , 52 osteoporosis, 52 dysfunctional breathing, 48 headaches, 39 and allergic status. 27 , 39 The consensus was that having an additional physical condition significantly decreased QoL in asthma, the effect being amplified with the addition of further conditions.

Eleven papers exploring BMI found that it consistently influenced QoL for people with asthma both directly as a multimorbid factor and indirectly by increasing the chance of additional conditions and activity limitation. 25 , 26 , 28 , 29 , 35 , 42 , 44 , 45 , 48 , 56 , 59 In particular, one study found that generic health status decreased for overweight and obese patients with asthma. People with asthma with obesity had on average 5.05 more restricted activity days than people without obesity or without asthma. 35 Other studies found that increased BMI was an independent factor in predicting poorer QoL 48 and that QoL was two times worse in overweight and three times worse in obese people with asthma. 59 In contrast, one study found that overweight BMI made no difference; however, being obese did. 27 Almost ½ of obese patients and 25% overweight patients had problems with mobility, pain, discomfort, self-care, and usual activities (compared to <15% people with asthma of normal weight). 26

Multifactorial aspects

Seven studies included statistical analyses to explore potential mechanisms for the relationship between asthma QoL and additional physical conditions, BMI, and psychological factors. 17 , 35 , 42 , 45 , 50 , 56 , 59 Results from studies in this group are complex, indicating that people with asthma are at a higher risk of adverse outcomes (such as exacerbated symptoms or decreased QoL) if they also have a high BMI and depression. 35 , 42 , 56 , 59 People with current depression and asthma are more likely to be obese and 3.9 times more likely to report fair or poor general health. 45 A few of these studies have explored the relationship between these factors further. For example, people with asthma and obesity were more likely to have additional physical comorbidities and poorer QoL. 59 Significant increases in major depression were associated with dyspnoea, 50 and depression and perceived control of asthma significantly mediated between BMI and QoL. 35 Higher BMI has also been associated with worse asthma-specific self-efficacy, which was in turn associated with decreased QoL. 42

The aim of the present review was to synthesise the literature exploring health and psychological factors that influence QoL in adults with asthma. Previous evidence shows that QoL is generally lower in people with asthma and compounded by poor asthma control and severity. 13 The narrative synthesis in the present study builds on this by identifying three themes, encompassing a number of factors that substantially explain further impairment in QoL for people with asthma. These were not limited to individual components but also combinations of co-existing conditions, risk factors, and health and psychological factors, which consistently showed a negative impact on QoL.

Anxiety and depression were the most commonly reported psychological factors associated with impaired QoL, but effects were also found for other mental health conditions, illness representations, and emotion regulation. These results are generally consistent with previous research showing not only that among people with asthma there are more people with depression than without 8 but also with an increase in depression, the risk of asthma increased. 64 Although the relationship between anxiety and depression and asthma-specific QoL were not further considered in the primary sources, they point towards either a link with activity limitation or a cumulative impact of the interaction between these psychological factors, which in turn affect the QoL of people with asthma. In addition, it is argued that people with asthma use more emotion-focused, and generally maladaptive, coping strategies, such as avoidance. 65 Despite this, psychotherapy, such as cognitive-behavioural therapy and counselling has had limited effectiveness in improving asthma outcomes. 66

Physical health factors, such as high BMI and co-occurring health conditions, were extremely common in people with asthma, consistent with existing literature. 16 This affects QoL both directly and indirectly, affecting self-management and illness perceptions. As such, non-pharmacological treatments such as lifestyle change and activity promotion could prove effective. For instance, a higher proportion of people with asthma seem to have overweight or obese BMI 67 and weight loss intervention studies have been associated with improvements in asthma symptoms. 68

One of the fundamental components of reduced QoL is activity limitation, which is especially relevant to people with asthma, with or without additional conditions or psychological risk factors. This has been widely acknowledged by previous research, to the extent that it has been included as one of the components of asthma-related QoL measures, such as the AQLQ. 69 Furthermore, it is not surprising that decreased QoL in adults with asthma is associated with depression or high BMI, both of which have been consistently associated with activity limitation (e.g. refs 70 , 71 ). In addition, depression was found to affect QoL on the physical components as well as the mental ones, which has interesting implications for future research and clinical practice.

It is important to note the high prevalence of anxiety, depression, and chronic conditions, despite frequent exclusion of comorbid psychiatric conditions. This was found throughout the included papers and is consistent with previous research (e.g. refs 8 , 16 ). This does not only mean that psychological and health factors significantly add to the burden of living with asthma but also that the occurrence of psychological dysfunction and health risk factors seem to be common in people with asthma. In addition, the complex nature of patients with chronic diseases such as asthma, with factors interacting, adds to the negative experience of living with asthma. Results are similar to previous meta-analyses and reviews, 8 , 72 pointing towards conclusive evidence that additional factors (physical or psychological) decrease QoL and functionality in asthma. Finally, these effects were consistent, regardless of the measure of QoL used (asthma specific, health related, or general). This suggests that the identified factors may affect people with asthma more than people without asthma or that the cumulative impact of comorbidities is greater than arithmetically assumed.

The quality of the present review needs to be discussed in relation to the methodology and robustness of the synthesis, determined by the quantity and quality of individual studies included. 73 The quality assessment identified that most studies were of a reasonable quality overall, although all papers had one or two elements that were of a slightly lower quality (this included aspects such as recruitment from only one hospital reducing generalizability or self-report vs objective measurement of weight for BMI calculations). However, this was not problematic for the purposes of this review as the focus was to identify potential factors considered in research rather than classify the methodological quality used to measure their impact on QoL. In addition, the search terms in this review could have limited the number and kind of studies included. For instance, not every potential comorbid condition was listed. This could be a focus for future research. Socio-demographic factors were not included, which can be considered a limitation; however, the breadth of the area was deemed too much for the scope of the present review and could also be the focus of future research. The majority of included studies were observational and as such could not be used to determine causal mechanisms. However, the aim of this review was only to identify potential factors involved in decreased QoL in asthma, rather than build a causal model. Similarly, the impact of individual factors was not measured and could be explored in future research.

A strength of the present review is that it uses a novel approach to QoL in asthma, by systematically taking into account additional aspects that influence the experience of living with asthma and impact QoL. Results suggest both a direct association of the identified aspects, as well as indirectly through interactions with other aspects of living with asthma, such as overarching illness perceptions and activity limitation. The present review emphasizes some interesting and novel findings for asthma and QoL research. Three main implications for future research and practice are proposed. First, for future research, the findings of this review should be used to further explore and understand the factors impacting QoL in people with asthma. It is crucial to explore the needs and experience of patients with complex medical problems, in order to unpick the different factors impacting on QoL. Second, the results are relevant for practitioners, particularly in primary care, as they draw attention to the prevalence of various physical and mental health factors that can interact and affect asthma outcomes. This could influence training or guidelines on potential factors to consider during appointments and consultations. Finally, most current non-pharmacological interventions for patients with chronic conditions tend to overlook the complex needs of patients in a multimorbidity context. As such, it is suggested that future intervention development should use a personalized, tailored approach that aims to address the needs of patients with complex medical problems in the wider context of their experience of living with asthma.

This review demonstrates that the themes and factors identified through inductive narrative synthesis illustrate that QoL in asthma cannot be determined in a simplistic way. The findings suggest a complex experience in living with asthma, one that has a stronger impact on QoL than the sum its of parts. People with asthma and their QoL cannot be viewed separately from the psychological and other health elements that they experience. Future research is encouraged to take a function-oriented approach to QoL in asthma, including management of multimorbid conditions when planning studies; clinical practice should also acknowledge the additional and complex needs of people with asthma by offering relevant, person-based tailored interventions.

Search strategy

The initial search was carried out in April 2017 and was updated in January 2019. Databases searched included MEDLINE, EMBASE, PsycINFO, the Cochrane Library, and Web of Science. Search terms used comprised a combination of the following key terms: asthma (MESH term), psychological/psychosocial and factor/determinant/predictor, comorbid, multimorbid, anxiety, depression, illness perception, illness cognition, illness representation, locus of control, self-efficacy, risk factor, quality of life, health-related quality of life, wellbeing, distress, health status, burden. In addition, a hand search of all the references of included papers was performed as well as a grey literature search on Google Scholar.

Study selection

Studies were included if they investigated psychological or physical health factors and included QoL in adults with asthma as primary or secondary outcome. Psychological factors were considered any modifiable factors, including thoughts, beliefs, attitudes, or emotions of people with asthma, as well as the presence of any co-occurring mental health condition. Physical health factors were defined as any physical comorbid or multimorbid condition or risk factor. These were chosen to allow as much inclusivity as possible and to reflect the exploratory nature of this review. Intervention studies were excluded, as they rarely considered the impact of health or psychological factors on QoL but rather investigated how interventions improved asthma outcomes. Studies were excluded if they were conference abstracts, reviews, or not primary research or the full text not in English, German, or Spanish language.

Data extraction and quality appraisal

Data extracted comprised authors, year of publication, study sample, predictors, QoL measurement (outcome), and findings. The AXIS tool 74 was used to assess the quality of included papers. This contains questions on study design, sample size justification, target population, sampling frame, sample selection, measurement validity and reliability, and overall methods and does not offer a numerical scale. No papers were excluded or weighted based on the quality assessment.

Data synthesis

Owing to heterogeneity of QoL measures and the range of variables used in the included studies, narrative synthesis was used to describe and group similar findings, explore patterns identified in the literature, and develop a narrative account of the results. 73 This is an approach to systematic reviews involving the synthesis of findings from multiple sources and relies primarily on word and text to summarise the findings.

All data generated or analysed during this study are included in this published article.

Reporting summary

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

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Stanescu, S., Kirby, S.E., Thomas, M. et al. A systematic review of psychological, physical health factors, and quality of life in adult asthma. npj Prim. Care Respir. Med. 29 , 37 (2019). https://doi.org/10.1038/s41533-019-0149-3

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Asthma History, Current Situation, an Overview of Its Control History, Challenges, and Ongoing Management Programs: An Updated Review

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Asthma is a disease of the airways that is characterized by chronic inflammation and disordered airway function. The purpose of writing the current review paper is to review the history, current situation, control history, challenges, and ongoing management programs of asthma. Some official websites of known respiratory professional bodies were consulted for asthma guidelines, and information from Google Scholar® and PubMed® was also consulted. We reviewed around two hundred eight papers, and then, inclusion and exclusion criteria were applied to prepare this manuscript. Out of these papers, thirty papers, factsheets, and some official websites were used to prepare this manuscript. Physicians should follow already existing asthma guidelines in order to manage asthma. All prescribed medications should be continued. The government should make and adopt more strategies to promote the rational use of anti-asthmatic drugs and healthcare facilities and also make plans to disseminate more awareness among people about the schemes and programs made for safeguarding people against this life-threatening disease. We have done so much advancement to fight against this deadly disease, and we still need time to make the globe asthma-free. The number of people suffering from asthma is more than the number of people suffering from HIV infection and tuberculosis. Understanding the recommendations of professional bodies will assist in medical decision-making in asthma management. The individual needs of patients should be considered by healthcare professionals.

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Asthma: Pathophysiology, Current Status, and Therapeutics

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Introduction

Asthma is one of the most ancient diseases of the airways, characterized by chronic inflammation and disordered airway function [ 1 ]. Despite numerous advancements in the treatment and diagnosis of asthma, unfortunately, a large population is still suffering, and worldwide it becomes one of the top infectious diseases. Approximately 10% of children and 5% of adults are suffering from this disease. A WHO key facts dated May 3, 2021, on asthma stated that approximately 262 million people are affected by this life-threatening disease in 2019 and the number will be expected to hike in the future. It is also characterized by some other symptoms like epithelial rupture, hypertrophy of airway smooth muscles, hypersecretion of mucous in lungs bronchial walls, wheezing, coughing, and dyspnea (Fig.  1 ). Although there is no proper treatment available for asthma, it can be controlled with proper management and help asthmatics to live in a better way [ 2 ]. The primary preventive measure taken by WHO (world health organization) for asthma and disease management is reducing tobacco smoke exposure, and the initiative MPOWER and Mtobacco cessation is enabling progress in this area of tobacco control.

figure 1

Flowchart of asthma

The use of bronchodilators is the principal therapy used in asthma but a greater understanding of the chief role of inflammation in asthma has led to the conclusion of the use of anti-allergic or anti-inflammatory agents for the management of asthma and is an internationally recognized strategy for its cure. The ICS (Inhaled corticosteroids) can provide ideal disease control but not as monotherapy. They need additional therapies such as SABA (Short-acting β2 agonists), LABA (Long-acting β2 agonists), LTRA (Leukotriene receptor antagonist therapy), and theophylline to achieve adequate control [ 3 ]. The primary aim of writing this review paper is to provide a brief understanding of asthma by critically assessing articles related to asthma.

Material and Methods

We performed an electronic search to find out the existing literature on asthma. Initially, the search was conducted on search engines like Google Scholar® and PubMed® to gather updated information about asthma. In addition, the search was conducted on the official websites of professional organizations such as GINA (Global initiative for asthma), WHO, MOHFW (Government of India-ministry of health and family welfare), and CDC (Centers for disease control and prevention) to get relevant guidelines for asthma control, anti-asthmatic drugs, challenges, prevention, and control management programs. Approximately 10 months were completely used to compile data for this manuscript. The key terms used during the search were “Asthma,” “history of asthma” “current situation of asthma,” “asthma control history,” “challenges in asthma,” and “ongoing asthma management programs.” Two hundred eight papers were screened, and then, inclusion and exclusion criteria were applied to prepare this manuscript. Out of these papers, thirty papers were used to prepare this manuscript. The last search was conducted on October 30, 2021.

Inclusion and Exclusion Criteria

Resources that were targeted at healthcare professionals and articles with a thorough understanding of asthma were included. All those papers which do not have original data and studies targeting the general public and patients were excluded.

Ancient History

For the very first-time, respiratory distress was recorded in China in 2600BC. The evidence was found in the form of “noisy breathing.” Shen nong in 2700BC was the first person to taste ephedra which was popularly known as anti-asthmatic herbal medicine around 5000 years ago [ 2 , 3 ]. The ancient Egyptians in 3000–1200BC believed respiration was one of the most crucial functions of the human body. Greco-roman (1000BC–200AD), both believe that asthma was produced due to demonic possession. Hippocrates was the first person who found that people suffering from asthma may have a hunch back. He also tried to understand the correlation between environment and respiratory problems. He also recommended ephedra along with red wine for the treatment of asthma [ 4 ].

Modern History

In the modern period, the understanding of the root cause of asthma began. In Europe 1500s, tobacco was introduced for the treatment of asthma, expectorate mucus and induce coughing. In 1579–1644, one of the chemists and physicians from Belgium Jean Baptiste Van Helmont said, “asthma was developed in the pipes of the lungs.” In (1633–1714), Bernardino Ramazzini found for the first-time exercise-induced asthma. He also acknowledged the correlation between organic dust and asthma. In the year 1873, Charles Blackley discovered the main cause of “hay asthma” and found that pollen was related to it. He rubbed pollen on different body parts to reproduce the symptoms [ 5 ]. In the 1900s, selective beta-2 adrenoceptors agonists were used for asthma treatment. In 1916, a physician and allergist named Francis Minot Rackemann reported that not all asthma is related to allergies. In 1920s, the deaths from asthma were related to airway structural changes and extensive inflammation but the information on why this happened and how it is responsible for bronchospasm was not known. For some decades, the treatment of asthma was done as episodic exacerbations [ 6 ]. Kustner and Prausnitz in the year 1921 noticed that asthmatics suffer from allergy symptoms due to indoor and outdoor irritants. In 1960s–1970s, technological advancements led to the use of peak flow meters to measure obstruction in airways and arterial blood gasses [ 7 ]. After the 1970s, inhaled corticosteroids were used for asthma cure. In 1980s, a depth understanding of how an allergen exposure, affect the release of a chemical mediator from mast cell which results in allergic asthmatic response [ 8 ].

Global Scenario

According to WHO information, asthma is included among (NCD) non-communicable diseases which is prevalent in children and adults. Generally, the deaths related to this disease mostly occur in countries with the economy in creeping and walking stage. The top fifteen countries with the largest asthmatic patients are Myanmar, Kiribati, Laos, Sri Lanka, New Guinea, Mali, Nepal, Fiji, Lesotho, Indonesia, Solomon Island, Sierra Leone, Timor-Leste, Philippines, and Vanuatu ( https://www.worldlifeexpectancy.com/cause-of-death/asthma/by-country/ ). In 2010, according to the data provided by National Hospital Ambulatory Medical Care Survey, approximately 1.3 million patients hospital visits were due to asthma [ 9 ]. In 2011–2012, the national survey for children’s health reported that around 3.4% of children have used emergency hospital visits due to this life-threatening disease [ 5 , 8 ]. Around 10.1 million physician office visits were reported for the year 2015. In 2017, around 43.12 million asthma cases were recorded whereas 272.68 asthma prevalence (prevalence 3.57%) and 0.49 million deaths (mortality rate 0.006%). More than 1.6 million asthmatic patient emergency visits were reported for the year 2018. According to the 2019 data by WHO, this disease is considered one of the top ten deadliest diseases. It cannot be completely cured but proper management with inhaled medications can help to control the disease and thereby help people to lead normal life [ 10 ]. Around 262 million people were affected by this deadly disease in 2019 which caused 461,000 deaths. Globally, this disease is ranked 16th among the leading causes of years lived with a disability as well as 28th among the leading causes of burden of disease as calculated by DALY (disability-adjusted life years). It is estimated that around 300 million people were suffering from asthma worldwide and by 2025 around 100 million people were affected. There is a huge geographical variation in asthma severity, prevalence, and mortality. The prevalence is extremely high in high-income countries whereas the mortality rate is high in low-middle-income countries. As per the Lancet, the asthma statistics worldwide for 2020 reported that more than 339 million people were suffering from asthma and globally approx. four million children develop asthma each year. In North America, approx. 8% population has been diagnosed with asthma. The estimated prevalence of severe asthma is 5–10% of the global asthma population. It is more common in Puerto Rican Hispanic (13.3%) and Black (8.7%) than in white people (7.6%). The mortality rate is higher in black 25.4 than in whites 8.8 per million annually. The treatment options available for asthma are discussed as follows:

Bronchodilators or relievers act by quickly opening the airways and improving the rate of breathing. They also remove mucous from the lungs. As the airways get dilated, the mucous can be coughed with more ease. These act by targeting the β-2 adrenergic receptors in the airways. Activation of this receptor may relax the airway smooth muscles, thereby ensuring better airflow in the lungs [ 11 ]. Furthermore, they also help in inhibiting the parasympathetic nervous system receptors from functioning. As the parasympathetic nervous system increases the bronchial secretions and constriction in airways, inhibiting the nervous system should result in bronchodilation and lesser bronchial secretion [ 12 ] (Fig.  2 ). Bronchodilators are subdivided into the following parts (Fig.  3 ), Inhaled rapid-acting β-2 agonists: Fenoterol (1), Salbutamol (2), Isoproterenol (3), Metaproterenol (4), Terbutaline (5), Albuterol (6), Glucocorticoids (systemic): Beclomethasone (7), Prednisone (8), Triamcinolone (9), Budesonide (10), Flunisonide (11), Anticholinergics: Tiotropium bromide (12), Ipratropium bromide (13), Atropine methonitrate (14), Oxitropium bromide (15), Xanthine derivatives: Caffeine (16), Theobromine (17), Theophylline (18), Aminophylline (19), Hydroxyethyl theophylline (20), Choline theophyllinate (21), Doxophylline (22), Deriphylline (23), Diprophylline (24), Theophylline ethanolate of piperazine (25), Oral SABA: Salbutamol (2), Terbutaline (5), Bitolterol (26), Fenoterol (27), Rimiterol (28), Levalbuterol (29), and Pirbuterol (30).

figure 2

Mechanism of action of bronchodilators in asthma

figure 3

Anti-asthmatic drugs used as bronchodilators

Anti-inflammatory agents reduce inflammation, swelling, and mucus production in the airways. The most important anti-inflammatory treatments are given by inhalation. Their mode of action is not completely understood, but they are likely to act in several different ways to produce an anti-inflammatory effect. The glucocorticoids act by inhibiting transcription factors that help in the regulation of pro-inflammatory mediators such as eosinophils, macrophages, dendritic cells, mast cells, and lymphocytes [ 13 ]. The steroids also act on mast cells and exert their anti-allergic action by inhibiting the signaling pathways in mast cells [ 14 ]. Furthermore, they also reduce plasma exudation in the airways and inhibit mucus glycoprotein secretion (Fig.  4 ). Anti-inflammatory agents are further classified into (Fig.  5 ), Inhaled or systemic corticosteroids: Triamcinolone (31), Mometasone (32), Budesonide (33), Prednisolone (34), Hydrocortisone (35), Beclomethasone (36), Fluticasone (37), Ciclesonide (38), Flunisolide (39), prednisone (40), Methylprednisolone (41), LABA: Formoterol (42), Salmeterol (43), Anti-IgE: Omalizumab, Leukotriene antagonist: Zafirlukast (44), Montelukast (45), Pranlukast (46), Iralukast (47), Oral anti-allergic compounds: Tranilast (48), Mast cell stabilizer: Sodium cromoglycate (49), Nedocromil Sodium (50), and Ketotifen (51).

figure 4

Mechanism of action of corticosteroids on airway inflammation, symptoms and airway hyper-responsiveness

figure 5

Anti-inflammatory drugs used for asthma

Indian Scenario

The Indians ayurveda believe that asthma results due to the imbalance between three doshas: (a) pitta (bile), (b) Kapha (phlegm), and (c) vata (wind). A person stays healthy if these three humors were balanced. The first book Ayurveda Materia medica from India ‘Charaka Samhita’ has a good clinical description of this life-threatening disease. A recent study on respiratory symptoms and chronic bronchitis performed on 85,105 men and 84,470 women from eleven rural and twelve urban areas in India estimated the prevalence rate of asthma is 2.05% among those aged above 15 years with an estimated national burden causing 18 million asthmatics [ 15 ]. Despite enormous advancements in the treatment and management of this disease, it becomes a major public health issue in India.

Asthma Control History

The early period of asthma control.

In 1500BC, the inhalation of the smoke of herbs is recommended for use as the treatment therapy for asthmatic patients in Egypt. In ancient China around 5000 years ago, the treatment was done by using ma-huang (Ephedra sinica), a type of Chinese herb which was later examined to have ephedrine (muscle relaxant), and these agents work as bronchodilators [ 6 , 13 ]. For a prolonged period, bronchodilators were used as the first-line drugs for the management of asthma which indicates contraction of airways as the chief pathology involved in the treatment. In 1900, the avoidance of allergens was used as the foremost therapy for asthma [ 5 ]. The use of a pressurized metered-dose inhaler in the mid-1950 has been developed for the administration of adrenaline and isoproterenol and was later used as a β2-adrenergic agonist. Later salbutamol and terbutaline were introduced as SABA. Recently, LABA is used as the principal drug incorporated into the inhaled corticosteroids in Japanese guidelines for asthma. Furthermore, LTRA and theophylline were used as the first-line drugs along with LABA and inhaled corticosteroids. The American thoracic society in the year 1962 describes asthma as a disease identified by the presence of airway hyper-responsiveness as well as reversible airway constriction [ 12 ]. Moreover, chronic airway inflammation was finally found as the clinical etiology involved in the pathogenesis of asthma and inhaled corticosteroids and the use of anti-inflammatory drugs became the first-line therapy for asthmatic patients [ 16 ]. In the early twentieth century, inhalation and intravenous administration of anticholinergic drugs were regarded as the principal therapy for asthma [ 2 ].

Current WHO-Aided Asthma Control Program

For the prevention and control of asthma, this disease has been incorporated in the WHO global action plan as well as the UN (United Nations) 2030 agenda for the sustainable development. WHO has taken several actions to extend the diagnosis and treatment of this disease. The PEN (package of essential non-communicable) disease intervention was developed by WHO to support people with non-communicable diseases with the help of UHC (universal health coverage) [ 17 ]. The PEN includes rules for assessment, diagnosis, and management of asthma and (COPD) chronic obstructive pulmonary disease and includes modules on healthy lifestyles (Fig.  6 ) [ 18 ]. The primary preventive measure taken for asthma and disease management is reducing tobacco smoke exposure, and the initiative MPOWER and Mtobacco cessation is enabling progress in this area of tobacco control. MPOWER is the WHO framework convention on tobacco control, and its guidelines were meant for countries working toward tobacco control. These guidelines were introduced in the year 2008 to manage tobacco control at the country level.

figure 6

Assessment of asthma as per WHO PEN

WHO Global Action Plan 2013–2020

The goal of this action plan is to reduce the number of morbidities, mortality, and disability due to NCD by using multisectoral cooperation and collaboration at distinct levels (national, regional, and global), so that the population will remain at the highest standard of health and productivity at all ages as well as those diseases will no longer act as a barrier to well-being. As per the WHO, the total number of deaths due to NCD may increase to 55 million by 2030. The scientific knowledge demonstrates that the prevalence of non-communicable diseases is greatly decreased if cost-effective preventive and curative action, as well as interventions for prevention and control of NCD which are already available, are implemented in a balanced and effective manner [ 19 ].

GINA Global Strategy for Asthma 2021

On Nov 1, 2021, the GINA published an executive summary of an updated evidence-based summary for the treatment and prevention of asthma. On Oct 18, 2021, the summary was published online. The GINA science committee was developed in the year 2002 to review published research on asthma. This GINA report is updated every year and approx. 500,000 copies of GINA reports were downloaded each year by one hundred countries [ 20 ]. GINA report has been updated in the year 2020 with some modifications such as interim guidance about asthma and Covid-19, additional information for the new as well as existing therapies; additional documents have been added in supporting the use of ICS (Inhaled corticosteroid)—formoterol in mild asthma; assessment of symptom control and new data have been incorporated for the initial treatment of newly diagnosed asthma; information related to a maximum daily dose of ICS-Formoterol has been added; additional documents for the support of the use of ICS and addition of minimum and maximum doses of ICS have been incorporated in the treatment recommendation for asthma, and new additional information about the management of asthma in children has also been added [ 21 ].

India Asthma Report

As per demographics, around 6% of children and 2% of adults were suffering from this disease. A maximum number of people in India have no health insurance, and there is a big gap in healthcare facilities for the poor and the rich people. Most of the medications available in India (inhaled corticosteroids, combination inhalers, and β-2 agonists) are too expensive compared to oral formulations [ 22 ]. According to the data compiled from 1990 to 2005, the mortality rate in India decreased mainly in areas where healthcare facilities were better (urban areas and prosperous states). It was documented that Rajasthan and Uttar Pradesh have the highest mortality rate. The Rajasthan government had provided free access to medicines to all the asthmatic patients of the state at government hospitals since 2011 and around 15,000 pharmacies had been opened by the state government across the state along with a free supply of metered-dose inhalers, nebulizer solutions, and dry powder inhaler capsules to asthmatic patients. In 2018, the Indian government planned to provide health insurance at no cost to 100 million low-income families, to cover their treatment costs [ 23 ].

Ongoing Challenges in Asthma Therapy

The problem of asthma is a global burden affecting more than 300 million people and causing around 2,50,000 deaths per year. Despite several effective treatments available, the control of this disease in the population remains inadequate. The advancement in treatments for children is lesser as compared to the adults due to the varying immunopathology, respiratory pathology, need for a child, parent education, and communication barrier. As most of the asthma research work was performed on adult asthma, thus this seems to be one of the principal barriers to managing the therapy childhood asthma [ 16 ]. The data on LABA use for the treatment of asthma in adults are widely available while the data available for LABA use in children are limited. Since then, several studies have been conducted to complete the gap for LABA use in children and adolescents resulting in several regulatory approvals for LABA inhalers, and inhaled corticosteroids such as fluticasone + salmeterol, budesonide + formoterol have been approved as maintenance treatment for children and adolescents in the USA and Europe [ 24 , 25 ]. Asthma management in children is a complex process due to variability in asthma severity, control, and difficulty in measuring lung function as well as airway inflammation. The primary challenge in the management of pediatric asthma is treating the symptoms of asthma rather than treating the root cause, i.e., inflammation, and switching to controller therapy when the problem worsens. The prevalence of childhood asthma increased in the 1980s–1990s, and the rate kept on increasing over the past decade; it seems to be one of the greatest global economic burdens in terms of direct and indirect costs.

Furthermore, the healthcare providers, as well as patients, are dealing with several types of challenges such as challenges in diagnosis, treatment, and follow-up challenges. As poor healthcare facilities are provided in rural areas, poverty, lack of awareness, and the high price of anti-asthmatic drugs are some of the routinely faced challenges of patients [ 26 ]. The diagnosis of asthma seems to be challenging work, both in terms of underdiagnosis and overdiagnosis. The underdiagnosis of asthma is familiar and was documented in epidemiological as well as clinical studies while the data on overdiagnosis are new [ 27 ]. Physicians are entirely dependent on asthma guidelines for the diagnosis and management of this disease. The NIH (National Institute of health) released latest updates to the national guidelines meant for the diagnosis, management, and treatment of asthma. The guidelines were made to upgrade patient care and to support decision-making about asthma management in a clinical setting.

In India, the national rural health mission (NRHM) was implemented to improve primary healthcare facilities in rural areas, to improve the health status and quality of life of people living in rural areas, and to prevent and control communicable and non-communicable diseases. The diagnosis of asthma is a difficult process because for some reasons: (a) The signs and symptoms might not show during routine analysis, (b) unavailability of the standard diagnostic test—in clinical practice, spirometry and peak expiratory flow assessment are done to check the signs and symptoms, and (c) The guideline recommendation is not always compatible with the working systems in primary care. Some of the other treatment options which might help in improving asthma management and control are switching from relievers SABA to LABA along with a combination of inhaled corticosteroids as per the recommendation of GINA to make sure that the person with asthma receives an inhaled corticosteroid to get symptomatic relief whenever possible.

Ongoing Asthma Management Programs

The problem of asthma is prevalent among children and elderly people. In UK 1 in 14 adults are affected by this alarming condition. The national public health agency of the USA, i.e., CDC has made a self-management education (SME) program “Breathe well, live well” that helps those people with prevailing health conditions to feel better. The SME program helps people to strategize and develop the skills and confidence to tackle ongoing health conditions efficiently and help in dealing with the following conditions: cope with symptoms, communicate with doctors, manage fatigue, handle stress, manage medication, eat healthy, reduce depression, and be active. These strategies can help the patients to make good decisions about health and makes them feel better [ 28 ].

The 2020 focused updates to the asthma management guidelines were published for the diagnosis and management of asthma. These guidelines help the clinician integrate the new recommendation into clinical care. These are meant for individual patient management [ 29 ]. The Alameda County public health department (ACPHD) enabled community health services asthma start programs that help families of children with asthma by providing in-home case management studies. They provide education, support, and assistance in developing an action plan to address the needs of families where the child has asthma thereby helping in regulating it. The services provided by them is as follows: (a) education to families about the disease, several types of triggers, prevention of attacks, treatments, etc., (b) collaborating with daycare providers and schools to make sure asthma medication is accessible to every child, and moreover, supplying asthma-related education to all the school staff as well as daycare providers, (c) assistance with health insurance, housing, and employment, and (d) remote home inspections to find the triggers and causes of asthma [ 30 ].

Results and Discussion

Generally, the recommendations from different professional bodies suggest that physicians should follow the already existing guidelines for the proper management of this disease. The key points are as follows: bronchodilators were considered a principal therapy for the treatment of asthma in early times, but after the advent of inhaled corticosteroids, the therapeutic history gets drastically changed. The use of bronchodilators is the principal therapy used in asthma but a greater understanding of the chief role of inflammation in the pathogenesis of asthma has led to the conclusion of the use of anti-allergic or anti-inflammatory agents for the management of asthma. The ICS can provide ideal disease control but not as monotherapy. They need additional therapies such as SABA, LABA, LTRA, and theophylline to achieve adequate control.

It is very much clear from the above discussion that we have done so much advancement to fight against this deadly disease and we still need time to make the globe asthma-free. The number of people suffering from asthma is more than the number of people suffering from HIV infection and tuberculosis.

Understanding the recommendations of professional bodies will assist in medical decision-making in asthma management. Healthcare professionals should consider the individual needs of patients. In conclusion, the main problem in the management of this disease is improper use of healthcare facilities, lack of knowledge about anti-asthmatic drugs, poverty, and the cost of drugs. The government should make and adopt more strategies to promote the rational use of anti-asthmatic drugs and make plans to spread more awareness among people about the schemes and programs made for safeguarding people against this life-threatening disease.

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Significance Statement: This review paper aims to spread awareness among the general public about the scenario of Asthma. The physicians should prescribe bronchodilators and anti-inflammatory agents to manage asthma symptoms.

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Kapri, A., Pant, S., Gupta, N. et al. Asthma History, Current Situation, an Overview of Its Control History, Challenges, and Ongoing Management Programs: An Updated Review. Proc. Natl. Acad. Sci., India, Sect. B Biol. Sci. 93 , 539–551 (2023). https://doi.org/10.1007/s40011-022-01428-1

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Received : 23 January 2022

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