Asthma in Preschool Children: A Review of the Diagnostic Challenges
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* Andrew J. Cave
* Lana L. Atkinson

## Abstract

Family physicians face many challenges when diagnosing asthma in preschool children. These diagnostic challenges are compounded by variations in the natural history of early stage asthma, which are not fully understood, since early childhood wheezing and asthma are heterogeneous disorders with many phenotypic and variable expressions. Since no standard definition for the type, severity, or frequency of symptoms exist for this age group, clear evidence-based recommendations are lacking. Without adequate guidance, family physicians are left to make diagnostic and treatment decisions, which can lead to undertreatment of asthmatics and overtreatment of transient wheezers. New guidelines that specifically address the challenges of diagnosing asthma in this particular age group (Global Initiative for Asthma, British Thoracic Society/Scottish Intercollegiate Guidelines Network) have recently been published, and researchers are actively seeking new methods and techniques through epidemiological studies to assist primary care clinicians in the diagnostic process. This review has wide application in primary care. By recognizing the diagnostic challenges and understanding the related best practices, family physicians will be better placed to treat, manage, and control asthma symptoms, resulting in lower morbidity rates and reduced health system costs, as well as enhancing the overall quality of life and well-being of the children affected.

*   Asthma
*   Child
*   Preschool
*   Diagnosis
*   Primary Health Care

Asthma is the most common chronic condition among children worldwide1 and is characterized by episodes of cough, wheezing, and shortness of breath; reversible airflow limitation; and bronchial hyperresponsiveness.2 Preschool-aged children (≤5 years old) suffering from this heterogeneous disorder, particularly those within underserved populations3 and minorities,4 frequently experience daytime fatigue and reduced activity levels, potentially hindering their developmental progress and diminishing social interaction.

To date, evidence suggests that early intervention is important.5,6 However, diagnosing preschool children is difficult and often results in undertreatment of asthmatics and overtreatment of transient wheezers.7,8 Therefore, a correct diagnosis is the first step toward effective treatment and management of asthma9 and thereby lowering potential harm due to misdiagnosis.10

This evidence-based review article presents many challenges associated with diagnosing asthma in preschool children. It also offers solutions to these challenges and identifies areas of research that are contributing to an improved understanding of the diagnostic process. It is hoped that this information will help facilitate the accurate and timely diagnosis of asthma in preschool children in a variety of health care settings and geographic locations.

## Data Sources and Selection Criteria

We based this review on the Global Initiative for Asthma guidelines published in 2009 and 201211,12; the British Thoracic Society/Scottish Intercollegiate Guidelines Network *Guidelines on the Management of Asthma*, published and updated in 201213; the National Heart, Lung, and Blood Institute Expert Panel Report 3, *Guidelines for the Diagnosis and Management of Asthma*, published in 2007.5 We also included key publications by the World Health Organization.1⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓⇓–14 MEDLINE, CINAHL, and the Cochrane Library were searched for publications between 2007 and 2013, using the search terms *asthma*, *cough*, *wheezing*, *breathlessness*, *diagnosis*, *management*, *barriers*, *primary care*, *preschool*, and *childhood*. We also searched cited references using the Web of Science, as well as our personal research article archive, to investigate and review relevant publications. All published guidelines agree on the current need for (or lack of) a gold standard for diagnosing asthma in preschool children and the associated challenges and solutions therein.

## Why is Diagnosing Preschool Children with Asthma So Difficult?

Young children are particularly difficult to diagnose with asthma for a variety of reasons.15 First, the diagnosis is a clinical one, since there is no standard definition of the type, severity, or frequency of symptoms. The absence of a standard definition means that it is not possible to make clear evidence-based recommendations on how to diagnose asthma.8,11,13⇓⇓–16

Another challenge is that airflow limitation or airway inflammation, the main pathologic hallmarks of asthma, are difficult to assess in this age group.17 Lung function measurements that are key to diagnosing asthma in older children and adults are not reliable in young children.18 Consequently, diagnoses are largely based on reported symptoms, in contrast to diseases connected to organs or those identified with blood tests or scans (eg, cancer) or that can be related to causal factors (eg, certain bacteria, such as tuberculosis).19 These diagnostic challenges are compounded by variations in the natural history of the early stage of asthma, which are not fully understood because early childhood wheezing and asthma are heterogeneous disorders with many phenotypic and variable expressions.20

Many symptoms that support an asthma diagnosis in young children are not necessarily “asthma specific.” For example, cough and wheezing may be seen in healthy children or are characteristic of other pediatric diseases.21 Therefore, differentiating the symptoms of asthma from those of other diseases in otherwise healthy children relates not only to the presence and absence of certain symptoms but also to their frequency, severity, and pattern (seasonal and diurnal).22 Trigger factors and the age of the child must also be considered.18⇓⇓⇓–22 All such alternatives must be examined before a diagnosis of asthma is made.

Although it is known that asthma is a multifactorial disease that may have different expressions depending on family and medical history, lifestyle, and environmental exposures,23 uncertainties about the fundamental causes of asthma remain.12 Understanding the causes and risk factors that each child may be exposed to is important when making a diagnosis, particularly because morbidity and mortality differ between racial and ethnic groups, suggesting possible genetic predispositions.23 Also, inconsistencies in the delivery of asthma care exist. Although the underlying causes for such differences are complex, they relate in part to the interrelationships between poverty, cultural differences, access to and the quality of care, the difficulties in reducing exposure to allergens, and problems that patients and families may have in adhering to treatment regimens.23

Collectively, an implication of these challenges is that early childhood asthma is frequently misdiagnosed as chronic bronchitis, wheezy bronchitis, reactive airway disease, recurrent pneumonia, gastroesophageal reflux, or recurrent upper respiratory tract infections. Therefore, many infants and young children do not receive adequate or appropriate therapy.5 However, evidence on which to base any recommendations for young children is limited. There are many reasons for this, including the scarcity of objective end points and the difficulties associated with ethical issues in researching very young children.24

## What Is the Approach to Addressing These Challenges When Assessing for Asthma?

### Take a Careful History

Establishing an accurate family history can be useful in identifying patterns of inheritance, as well as recognizing long-term patterns of episodic respiratory signs and symptoms that could not be attributed to any alternative conditions.13,23 This symptoms-only descriptive approach, which recommends including various phenotypic definitions of wheezing, is an important component during history taking.7,11,17,25⇓–27 Identifying such patterns helps guide diagnostic, therapeutic, and preventive approaches.28

Epidemiologic studies have identified a number of factors about a child's history that should be obtained, including, but not limited to: 

*   timing and pattern of wheezing (either acute or chronic);

*   associated factors, such as the relationship of these episodes to viral illness and feeding and history of comorbid conditions;

*   response to previous treatments;

*   family history of atopic disease;

*   personal history of atopic disease;

*   social and environmental factors that seem to contribute to morbidity;

*   maternal diet during pregnancy and/or lactation; and

*   psychosocial factors.17,20

Clear, understandable, and culturally sensitive discussion between a clinician and their patient is a prerequisite for effective communication of symptoms during history taking.29 However, young children provide a special challenge in communicating symptoms, primarily because it is the parent who must often interpret their child's descriptions of the symptoms or the physical signs they observe and describe these symptoms to the clinician.

#### Patient-Centered Care: Engaging Preschool Children in the Diagnostic Process

Traditionally, clinicians generally exclude children younger than the age of 10 from discussions about their illness.30,31 However, the following recommendations may facilitate a better patient-centered care approach with children31: 

1.  Engage with children's expertise about their own lives, including their personal and social experiences of their care, as well as how these experiences are affected by their relative lack of power in some settings.

2.  Explore children's understanding and preferences in terms of their physical sensations and day-to-day experiences.

3.  Be willing to find resources to engage even the youngest children.

4.  Avoid age-based assumptions about children's contributions to their care.

These recommendations may present a range of challenges in health care settings, not least because they represent a move toward engaging with young children's experiences from their earliest ages.31 However, diabetic children as young as 4 years old were reported to actively monitor their diet, interpret physical symptoms, perform their own blood tests and insulin injections at the correct time, as well as explain their illness to others.31,32 Researchers who engaged with younger children also used a range of methods to help the children explain their illness. These included meeting children in comfortable, nonthreatening environments and providing them with materials to demonstrate, draw, or role-play their experiences.31⇓⇓⇓–35

However, challenges of implementing these types of patient-centered care in clinical practice include the extra time and resources needed to seek out young children's experiences.31 It may be difficult to justify these additional resources during times of funding pressure. Nevertheless, the extent to which a child's lack of engagement in health care settings affects their lives should not be overlooked.31 Considering these complex barriers has implications for practice, research, and policy changes that should be made.23

#### What About “Wheeze”?

Failure to treat a child's asthma appropriately may be due to a child's inaccurate description of their symptoms; ineffective communication with the clinician; inappropriate action by the clinician, the parent, or the child; or misinterpretation of the symptoms (such as wheezing) by the parent.29

Wheezing is a very common symptom in young children, as are upper respiratory tract infections. Therefore, all that wheezes is not necessarily asthma. Since development of asthma during childhood is highly variable and the common symptoms are so nonspecific, it follows that diagnosis and treatment are largely based on verbal interactions, with parents presenting the child's history of illness secondhand.19,36

Wheezing is one of a number of respiratory noises that occur in children and is defined as a continuous high-pitched sound with a musical quality emitting from the chest during expiration.7 It is important to distinguish wheezing from other respiratory noises such as stridor or rattly breathing.13,37,38 However, parents differ widely in their understanding of wheeze, with definitions ranging from a whistling, squeaking, or gasping sound to a different rate or style of breathing. Others think it is the same as cough. Consequently, parents often use “wheezing” as a nonspecific name for any abnormal respiratory noise,37 potentially resulting in the child being labeled and treated as a wheezer when he or she is not.7,39

The unreliability of parental recognition of wheeze has been recognized in studies using a video-based questionnaire40 or objective recording of lung sounds.41 The significance of these sounds is very different, and time must be spent when taking a child's history to determine exactly what the parent means.21,42 Therefore, the clinician's challenge is to ask good questions based on the typical pattern of asthma is preschool-aged children and in the context of the parents' vocabulary and understanding.43

#### Other Factors to Consider During History Taking

Because of divorce, fractured family relationships, or loss, it may be emotionally difficult for some to recount their family history.28 Alternatively, some children may have multiple family members caring for them, without a single adult assuming primary responsibility, so that establishing a complete family history becomes difficult.28

Maternal distress has been associated with the development of childhood asthma, so understanding the child's birth history is an important part of the diagnostic process.44 Dreger and colleagues45 investigated the association between children's cortisol concentrations and the combined predictors of exposure to maternal distress and childhood asthma. Among children exposed to recurrent maternal stress, Dreger et al found that an increase in cortisol concentrations occurs in response to an acute stressor when there is no diagnosis of asthma; however, children with asthma tend to exhibit lower cortisol concentrations. Similar results were reported by Wright et al.46 After evaluating an inner-city population, Wright and colleagues reported an association between prenatal stress and altered innate and adaptive immune responses to cord blood mononuclear cells. They suggested that stress-induced perinatal immunomodulation might affect the expression of allergic disease in children.

Brasholt et al47 studied the association between physical activity in preschool children and objectively assessed intermediary asthma phenotypes. They concluded that physical activity in preschool children was reduced with increasing bronchial responsiveness. This reduction was subclinical and not recognized by parents or doctors despite daily diary cards and close postnatal clinical follow-up. They recommended that increased recognition of even very mild, subclinical asthma symptoms is important.44,47

Proposed strategies for improving asthma care include the use of standardized screening questionnaires to assess symptoms using the modified Asthma Predictive Index (mAPI) and to predict likelihood using the Asthma Control Questionnaire and the Asthma Control Test. The Asthma Predictive Index (API) was derived from data from the Tucson cohort and developed to help clinicians identify those children who will continue wheezing into older childhood.20 The most impressive aspect of the API is its ability to determine the likelihood that young children with wheezing will develop asthma by school age.15,44

The API includes risk factors such as frequent wheezing, parental history of asthma, and signs of personal atopy.5,48 The API was recently modified, replacing the clinical diagnosis of allergic rhinitis with evidence for allergic sensitization20,49 (see Table 1). The mAPI has been described and endorsed by the Expert Panel Report 3, and although it is not prospectively validated, it might be a useful tool in identifying children who are more likely to have persistent wheezing and who might respond to inhaled corticosteroids. The sensitivity and specificity of the mAPI have yet to be determined.20

View this table:
[Table 1.](http://www.jabfm.org/content/27/4/538/T1)

Table 1. Modified Asthma Predictive Index (API) versus Original API*

Other strategies for improving care include more frequent routine visits for children with persistent symptoms; more widely disseminating realistic goals for symptom control29; and maintaining active dialogue so that information is readily available and shared.28 However, collecting accurate, detailed, and, when necessary, updated family information is time consuming.28 Lack of time often relates to parents who are working full-time or clinicians lacking the support or motivation to obtain the information.28

Despite constraints in applying family history information to primary pediatric practice, tools are available to assist clinicians with the efficient collection and application of this information.28 These tools can be tailored according to the needs of each family, as well as the strengths and challenges of the practice setting and patient population.28

### Perform a Thorough Clinical Examination

Asthma in young children can often be diagnosed by identifying symptom patterns by carefully assessing family history and performing a physical examination.50 The presence of atopy or allergic sensitization provides additional diagnostic criteria, since these symptoms increase the likelihood that a wheezing child has asthma,17,51 but a clinical examination is mandatory.

Even if a child is not experiencing any respiratory symptoms of distress at the time of the clinical examination, the physical examination is a useful component of the diagnostic process. A physical assessment can determine whether the child has an atopic disorder, as well as identify any physical signs (such as digital clubbing or a severe chest deformity) suggesting a more serious underlying diagnosis or a systemic disorder.52 Such examinations should be comprehensive and focus on both the upper and lower respiratory tracts, chest, and skin.20,53

Physicians also need to be aware of the complex, age-dependent relationships that may lead to differential diagnoses of wheezing during childhood, particularly because this possibility increases the younger the child is.8 It is also important that physicians broaden their differential diagnosis to help decrease the likelihood of diagnostic errors.10 Table 2 presents an age-related review of the differential diagnoses during infancy, childhood, and adolescence.20,54,55

View this table:
[Table 2.](http://www.jabfm.org/content/27/4/538/T2)

Table 2. Age-Related Differential Diagnosis for Wheezing

### What Is the Role of Lung Function Testing?

Although spirometry and tests such as airway responsiveness and markers of airway inflammation are used for diagnosing older children and adults, their use on young children is difficult, and several require complex equipment, making them unsuitable for routine use.12,20,56 In the past decade, however, a small number of studies were conducted to assess the feasibility of spirometry in young children.48,57 These concluded that spirometry is feasible in children 3 to 6 years of age and may be useful for clinical practice and research purposes.

Lung function testing, bronchial challenge, and other physiologic tests have a minor role in the diagnosing asthma in children <5 years old because of the child's inability to perform reproducible expiratory maneuvers.17 Nevertheless, children 4 to 5 years old can be taught to use a peak expiratory flow meter, although supervision is required to ensure reliability.12 For this age-group, however, spirometry would be more feasible if strict reproducibility criteria were not applied. Results showed that between 50% and 92% of 3- to 6-year-olds produced a minimum of 2 acceptable curves, with a margin of error of <10%.48,58⇓–60

There has been increasing interest in applying and developing lung function testing in young children. The American Thoracic Society (ATS) and European Respiratory Society (ERS) formed a Joint Expert Panel to review the feasibility and reliability of spirometry in young children. The Joint Panel published an official statement that acknowledged that the current repeatability criteria for adult spirometry are not appropriate for preschool children.57 They proposed modifying the criteria so that young children are required to produce at least 2 acceptable curves that are within 10% of each other. They also gave researchers and clinicians the option of accepting only one curve if there is no doubt that it was technically satisfactory.57

In addition, forced expiratory volume (FEV) can be measured over half a second (FEV0.5) as opposed to 1 whole second (FEV1). The Panel explained that FEV0.5 is physiologically more appropriate for young children because they have large airways relative to absolute lung volume compared to adults, and forced expiration is therefore completed over a shorter period.57

The ATS/ERS statement encourages clinicians and researchers to make accommodations for young children to obtain good results and improve reproducibility. The report suggests making the laboratory child friendly and offering adequate time to complete the tests using incentive spirometry software that is interactive and animated. The ATS/ERS outline areas for research and improvement that would make spirometry more reliable in young children and a better tool for clinical practice.48,57

### Closely Monitor and Evaluate Treatment Trials

A trial of treatment (at least 8 to 12 weeks) with short-acting bronchodilators and inhaled glucocorticosteroids for persistent asthma may indicate the presence of asthma.12 These interventions should be evaluated in terms of how they control daytime and nocturnal symptoms, as well as the effectiveness of increasing the dose of inhaled or systemic glucocorticosteroids on reducing the frequency of exacerbations. Identifiable clinical improvement during treatment and deterioration after discontinuing it supports a diagnosis of asthma.12,17 However, many children exhibit the seasonal/intermittent asthma phenotype, so repeated therapeutic trials may be needed to be confident of the diagnosis.17 For additional diagnostic tips for nonspecialists, see Table 3. However, when diagnosis is in doubt, especially in the early wheezer, specialist referral should be considered (see Table 4 for information on when to refer to a specialist).

View this table:
[Table 3.](http://www.jabfm.org/content/27/4/538/T3)

Table 3. Tips for Diagnosing Asthma in Preschool Children for Family Physicians

View this table:
[Table 4.](http://www.jabfm.org/content/27/4/538/T4)

Table 4. Situations in Which Specialist Referral Should be Considered When Asthma Diagnosis is Inconclusive

## Conclusions

Correct diagnosis is the basis for asthma care and is the first step in reducing the symptoms, effects on lifestyle, and risk of adverse effects that are associated with the disease.5 Diagnosis and intervention during the early stages of asthma is important, since the severity of lung function impairment is related to the duration of the disease.6 It is also important for health care professionals to recognize that despite some similarities, important differences exist between asthma in adults and children.13 These differences relate to natural history and comorbidities, and so it becomes important for the clinician to modify their approach according to the age of the patient. Therefore, care and attention must be paid to the special considerations of children, especially preschool-aged children.

However, perhaps the most important thing for primary practitioners to recognize is that they will encounter many children for whom a definitive diagnosis simply cannot be made, and the issues around under- and overtreating may never be resolved. Instead, the focus should be to establish a relationship built on trust whereby the lines of good communication are kept open during the treatment, management, and follow-up of the disease. This perhaps creates the best diagnostic outcome and therapy for the child.

### Future Directions

Although clinical approaches, predictive tests (eg, mAPI), and trials with bronchodilators or glucocorticosteroids are still helpful, new avenues to early diagnosis and treatment may include adopting epidemiologic research, which focuses on more accurate phenotypic approaches.8 Furthermore, the development of new diagnostic tools (eg, nitric oxide testing) in recent years, such as the identification of volatile organic compounds in exhaled breath, have helped distinguish between asthma and transient wheezing.8,61 For example, the Asthma Detection and Monitoring Study is developing a noninvasive instrument to monitor inflammation in young children (2 to 3 years old) using exhaled inflammatory markers and early lung function measurements. It will potentially avoid both overtreatment of children with transient wheeze and undertreatment of children with asthma.62

Induced sputum testing also has potential for being a useful tool; however, it is technically demanding as well as time consuming, which is why it currently is not recommended in clinical practice.8,63,13 See Table 5 for other ongoing and emerging research efforts.

View this table:
[Table 5.](http://www.jabfm.org/content/27/4/538/T5)

Table 5. Ongoing and Emerging Research in the Diagnosis of Asthma in Preschool Children

In the primary care setting, effective asthma care for children should extend beyond a traditional biomedical model based on current guidelines to a more holistic and comprehensive (rather than episodic) approach that incorporates an ongoing assessment of the family's environment and socioeconomic status and their willingness to engage in and adapt to diagnostic and treatment regimens.23 Furthermore, diagnostic approaches require demographic adaptations that consider variations in health care resources within different clinical practice settings.11

Despite these promising approaches and innovative tools, some level of uncertainty in diagnosing asthma in preschool children in general practice settings likely exists.8,22 However, these uncertainties can be reduced using effective interventions that recognize the challenges of diagnosis and extend beyond routine health care by providing the necessary investment in social and community resources. These interventions involve behavioral and lifestyle changes, increased educational resources (Table 6), provision of adequate housing, and environmental reforms.23,67

View this table:
[Table 6.](http://www.jabfm.org/content/27/4/538/T6)

Table 6. Educational Resources for Physicians and Parents Caring for Preschool Children with Asthma

Through our comprehensive review of numerous national and international practice guidelines and evaluation of the most up-to-date evidence, we conclude that demographic variations based on socioeconomic conditions, genetic diversity, cultural beliefs, and differences in health care access and delivery influence the diagnostic approach of clinicians.18 By understanding these best practices and recognizing diagnostic challenges, health care providers will be better placed to treat, manage, and control asthma symptoms, resulting in lower rates of morbidity and reduced health system costs, as well as enhancing the overall quality of life and well-being of the children affected.

## Acknowledgments

The authors thank Christine Graf for her contribution during the initial search and retrieval of articles used in this review.

## Notes

*   This article was externally peer reviewed.

*   *Funding:* none.

*   *Conflict of interest:* none declared.

*   Received for publication October 18, 2013.
*   Revision received March 17, 2014.
*   Accepted for publication March 24, 2014.

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    [Abstract/FREE Full Text](http://www.jabfm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpjbiI7czo1OiJyZXNpZCI7czo4OiI4NS8zLzg1MyI7czo0OiJhdG9tIjtzOjIwOiIvamFiZnAvMjcvNC81MzguYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

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    [Abstract/FREE Full Text](http://www.jabfm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiYWpjbiI7czo1OiJyZXNpZCI7czo4OiI4NS8zLzc4OCI7czo0OiJhdG9tIjtzOjIwOiIvamFiZnAvMjcvNC81MzguYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

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    [Abstract/FREE Full Text](http://www.jabfm.org/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MTA6InBlZGlhdHJpY3MiO3M6NToicmVzaWQiO3M6OToiMTA5LzUvOTE5IjtzOjQ6ImF0b20iO3M6MjA6Ii9qYWJmcC8yNy80LzUzOC5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=)