Asthma is a prevalent respiratory condition affecting millions worldwide, yet its diagnosis remains a complex challenge for healthcare professionals. While concerns about over-diagnosis have gained traction, the issue of under-diagnosis in asthma presents a significant, often overlooked, threat to patient health and well-being. This article delves into the critical problem of asthma under-diagnosis, exploring its prevalence, underlying causes, and the potentially severe consequences for individuals and healthcare systems. We will examine why recognizing and addressing under-diagnosis is paramount to improving asthma management and patient outcomes.
Asthma, characterized by variable airflow obstruction and airway inflammation, manifests through symptoms like breathlessness, wheezing, chest tightness, and coughing. It is estimated to affect a substantial portion of the global population, with a prevalence of approximately 10% in Europe alone, equating to 30–50 million individuals [1]. The economic burden of asthma is also substantial, with direct healthcare costs in Europe reaching an estimated EUR 17.7 billion annually. Despite advancements in asthma management, the disease continues to be a cause of mortality, with a concerning number of asthma-related deaths reported each year [2].
Traditionally, asthma diagnosis has relied heavily on patient history and response to treatment trials. However, asthma symptoms are non-specific and overlap with a wide range of respiratory and non-respiratory conditions, as detailed in Box 1. Furthermore, physical examinations are frequently normal in asthma patients, particularly when they are not experiencing an exacerbation. The majority of asthma diagnoses occur in primary care settings, where access to comprehensive objective testing is often limited. Even when available, tests such as spirometry, fractional exhaled nitric oxide (FeNO), and bronchial provocation tests have limitations and may not definitively confirm or exclude asthma, especially if conducted after treatment initiation. This diagnostic complexity contributes to both over-diagnosis and under-diagnosis, both of which pose significant risks to patient health and strain healthcare resources.
Diagnosing Asthma: Navigating the Challenges
Current asthma diagnostic guidelines emphasize the importance of objective testing to enhance diagnostic accuracy. The Global Initiative for Asthma (GINA) guidelines, widely adopted globally, advocate for objective measurements like spirometry before initiating asthma treatment, unless clinically urgent [4]. Similarly, the British Thoracic Society (BTS) and Scottish Intercollegiate Guidelines Network (SIGN) guidelines, prevalent in the UK and other regions, recommend objective tests for cases where diagnosis is uncertain [5]. The UK’s National Institute for Clinical Excellence (NICE) guidelines further underscore this by outlining a diagnostic protocol incorporating spirometry with reversibility [6].
Bronchial provocation tests, including direct challenges with histamine or methacholine and indirect challenges like exercise or hypertonic saline, are recommended by these guidelines when asthma is suspected but initial investigations are inconclusive. While often considered valuable, these tests can yield false positives in non-asthmatic individuals and false negatives in asthmatics, particularly those already on inhaled corticosteroids (ICS). Interpretation must therefore be individualized. GINA and BTS/SIGN support both direct and indirect challenge tests, whereas NICE currently recommends only direct provocation methods.
Another point of divergence among guidelines is the role of FeNO testing. NICE strongly endorses FeNO as a marker of airway inflammation, while GINA and BTS/SIGN offer less emphatic recommendations. This reflects ongoing debate within the respiratory community regarding FeNO’s utility. While FeNO can indicate type 2 airway inflammation, it is influenced by factors like diet, smoking, and comorbidities like nasal polyposis. The lack of clear normative values also complicates its interpretation.
These variations in diagnostic approaches highlight the absence of a definitive consensus on asthma diagnosis and differing perspectives on the value of FeNO and other type 2 inflammation markers [7]. Table 1 summarizes commonly used diagnostic tests in asthma and factors that can confound their interpretation.
The Hidden Burden: Under-Diagnosis of Asthma
While over-diagnosis of asthma is a recognized concern, under-diagnosis represents a less discussed yet equally critical problem. Failing to diagnose asthma can have profound implications for individuals, leading to untreated symptoms, increased risk of severe exacerbations, and long-term health consequences.
How Common is Under-Diagnosis?
Estimates of asthma under-diagnosis vary widely, ranging from 19% to as high as 73%. A large-scale study in Copenhagen involving over 10,000 participants aged 14–44 years found that among those diagnosed with “definite asthma” based on GINA guidelines, 50% were previously undiagnosed [15]. Similarly, a study in Italy reported that approximately 32% of individuals identified with asthma through questionnaires and objective testing had not received a prior diagnosis [16]. In the United States, research among young adults entering military service revealed that 30% of those diagnosed with asthma at enrolment had never been previously considered to have the condition [17].
These studies, while informative, often focused on younger age groups. Research in older populations further highlights the persistence of under-diagnosis across the lifespan. A study in the Netherlands involving individuals aged 65 years and older with respiratory symptoms found that a significant 70% of asthma patients in this cohort were undiagnosed [19]. This underscores that under-diagnosis is not limited to specific age groups and affects individuals across different demographics.
Why Does Under-Diagnosis Occur? Unraveling the Reasons
Several factors contribute to the concerning rates of asthma under-diagnosis. One key aspect is the non-specificity of asthma symptoms. Cough, breathlessness, and wheezing can be attributed to various conditions, leading healthcare professionals to overlook asthma, particularly in the absence of classic triggers or clear physical examination findings. Symptoms may be misattributed to obesity, deconditioning, cardiac issues, or other respiratory ailments. The absence of readily available and consistently applied objective testing in primary care further complicates accurate diagnosis. Even when tests are conducted, results can be misinterpreted, especially if performed when the patient is asymptomatic or already on asthma medication, potentially masking the underlying condition.
Furthermore, patient-related factors play a crucial role. A significant proportion of individuals with asthma symptoms simply do not report them to healthcare providers. The DIMCA project, focusing on early detection of asthma and COPD, found that 66% of patients with asthma symptoms and objective airflow obstruction, but no prior diagnosis, had never consulted their general practitioner about their symptoms [20]. This reluctance to seek medical attention may stem from a lack of awareness about asthma, normalization of symptoms, or poor perception of airflow obstruction. Research suggests that individuals with poorer perception of airflow limitation are less likely to present to their doctors with respiratory symptoms [20].
The Consequences of Under-Diagnosis: A Cascade of Adverse Effects
Under-diagnosed asthma translates directly to untreated asthma, initiating a cascade of negative consequences for patients’ health and quality of life. Persistent, uncontrolled symptoms can significantly impair daily activities, leading to exercise avoidance, reduced work productivity, and diminished sleep quality. Untreated airway inflammation, a hallmark of asthma, increases the risk of exacerbations, potentially requiring oral corticosteroids and even hospitalization [21].
In severe cases, under-diagnosis can have life-threatening implications. The UK national review of asthma deaths revealed that a concerning 38% of asthma-related fatalities occurred in patients who had received limited steroid inhaler prescriptions in the preceding year, suggesting undertreatment as a contributing factor [22]. Alarmingly, nearly half of the patients who died from asthma were being managed for “mild” or “moderate” asthma, highlighting the dangers of inadequate diagnosis and management.
Beyond immediate symptom burden and exacerbation risk, under-diagnosis can contribute to long-term airway remodeling. Prior to the widespread use of ICS, the natural progression of asthma often involved a decline in lung function over time [23]. Studies have shown that the duration and severity of asthma correlate with the degree of airflow obstruction [24]. Early intervention with ICS has been demonstrated to significantly improve lung function and alter the disease course [25, 26]. Under-diagnosis delays this crucial early treatment window, potentially missing the opportunity to prevent irreversible airway damage and long-term lung function decline.
Addressing Under-Diagnosis: Charting a Path Forward
Combating asthma under-diagnosis requires a multifaceted approach encompassing improved diagnostic strategies, enhanced public awareness, and proactive healthcare practices. Routine implementation of objective tests for airflow obstruction and bronchial hyperresponsiveness before initiating asthma treatment is crucial. Integrating measures of type 2 airway inflammation, such as FeNO, into diagnostic algorithms may further enhance accuracy and aid in identifying asthma phenotypes. Prospective evaluation of diagnostic algorithms incorporating these measures and improving access to objective testing in primary care settings are essential steps.
Public health campaigns aimed at raising awareness about asthma symptoms and encouraging individuals to seek medical attention are vital to address patient-related barriers to diagnosis. Screening for respiratory symptoms during routine primary care visits, such as when patients register with a new practice, could proactively identify individuals who require further asthma assessment. Educating healthcare professionals about the nuances of asthma presentation, the importance of objective testing, and the risks of under-diagnosis is equally critical to improving diagnostic rates and ensuring timely and appropriate asthma management.
Conclusion: Recognizing and Rectifying Under-Diagnosis
Asthma misdiagnosis, encompassing both over-diagnosis and under-diagnosis, is a pervasive issue with significant consequences for patient health and healthcare resource utilization. While concerns about over-diagnosis are valid, the problem of under-diagnosis warrants equal, if not greater, attention. The non-specific nature of asthma symptoms, limitations in diagnostic testing, and patient-related factors contribute to substantial rates of under-diagnosis across all age groups.
The ramifications of under-diagnosis are far-reaching, encompassing persistent symptoms, increased exacerbation risk, potential mortality, and long-term airway remodeling. Addressing this challenge necessitates a concerted effort to improve diagnostic accuracy through wider adoption of objective testing, enhance public awareness of asthma symptoms, and implement proactive screening strategies within primary care. By prioritizing the recognition and rectification of asthma under-diagnosis, we can strive towards better patient outcomes, improved quality of life, and a more effective approach to asthma management on a population level.
Footnotes
Conflict of interest: J. Kavanagh has nothing to disclose.
Conflict of interest: D.J. Jackson reports personal fees from Astra-Zeneca, Napp Pharmaceuticals, Chiesi Pharmaceuticals, and GSK, and non-financial support from Boehringer-Ingelheim and Teva Pharmacueticals, outside the submitted work.
Conflict of interest: B.D. Kent reports personal fees from Astra-Zeneca, Napp Pharmaceuticals, and Chiesi Pharmaceuticals, and non-financial support from Boehringer-Ingelheim and Teva Pharmacueticals, outside the submitted work.
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