Prevalence of Asthma-Like Symptoms in Young Children

Transcription

1 Pediatric Pulmonology 42: (2007) Prevalence of Asthma-Like Symptoms in Young Children Hans Bisgaard, MD 1 * and Stanley Szefler, MD 2 Summary. Objective To determine the prevalence, impact, and treatment of asthma-like symptoms in preschool children in USA and Europe. Study Design: 7251 households in USA and Europe with at least one child aged 1 5 years were interviewed by telephone for recurrent days troubled by cough, wheeze or breathlessness during the recent 6 winter months. Results: 9490 young children were identified, 32% of whom were reported to suffer from recurrent days with troublesome cough, wheeze or breathlessness. Detailed interview with the 2700 mothers of the symptomatic children showed that 24% of this interview population suffered weekly symptoms despite current treatment with considerable impact on lifestyle and healthcare resource use. Antibiotics, cough- and herbal-medications were the most commonly used treatments. Antiasthmatic and anti-allergy agents were prescribed in the order: inhaled b 2 -agonists > inhaled corticosteroid > oral anti-histamines > oral corticosteroids. The reported symptom burden was higher in Southern Europe and there were pronounced regional differences in treatment and diagnostic terms. Conclusions: Recurrent days with cough, wheeze or breathlessness in preschool children represents a major cause of morbidity in preschool children despite current treatment. There is a striking lack of international consensus on diagnosis and treatment. This uncontrolled morbidity highlights a significant unmet clinical need in preschool children. Pediatr Pulmonol. 2007; 42: ß 2007 Wiley-Liss, Inc. Key words: wheezing; cough; asthma; preschool children; respiratory symptoms; respiratory infectious diseases; survey; breathlessness. INTRODUCTION Childhood asthma is commonly preceded by recurrent asthma-like symptoms during the first years of life. This is the major cause of pediatric health care resource utilization with children below 5 years of age consuming 75% of the total pediatric inpatient resources for asthma management in the Scandinavian region. 1 This is partly due to a limited evidence base and lack of consensus on the diagnosis and management of young children with asthma-like symptoms. An increased awareness and understanding of such symptoms in young children is therefore needed. A questionnaire-based survey reported that 40% of children had experienced wheezing at some point during the first 6 years of life. 2 One of the difficulties facing such a survey is that wheeze does not exist as a term in all languages and even where it does it rarely conveys a specific meaning to lay people. 3,4 We therefore conducted a cross-sectional survey of a population of children aged 1 5 years (preschool children) in the USA and Europe to estimate the prevalence of recurrent troublesome wheeze, cough, and breathlessness emphasizing the severity and persistence of such lung symptoms as the salient feature of pathology rather than any specific term with the aim to improve understanding of the nature and burden of asthma-like symptoms. METHODS Survey Design The study comprised a telephone survey of nationally representative samples of households in the USA and six ß 2007 Wiley-Liss, Inc. European countries (Denmark, France, Germany, Italy, Spain, and UK). Selection of survey population is described in the on-line repository. The surveys were This article contains Supplementary Material available at interscience.wiley.com/jpages/ /suppmat. 1 Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, Copenhagen, Denmark. 2 Department of Pediatrics, National Jewish Medical and Research Centre, Denver, CO. Hans Bisgaard has been a Consultant to, paid lecturer for, and holds sponsored grants from, Aerocrine, AstraZeneca, Altana, GSK, MedImmune and Merck. He has no stock ownership or commercial royalties in the respiratory field. Stanley Szefler has Served as a consultant and member of an advisory board for GSK, AstraZeneca and Aventis for the past 3 years and for Merck for the past 2 years. He has received research funds for clinical trial performance from AstraZeneca and Ross. He has no stock ownership or commercial royalties in any of these companies. Grant sponsor: AstraZeneca R&D, Lund, Sweden. *Correspondence to: Hans Bisgaard, MD, Danish Pediatric Asthma Center, Copenhagen University Hospital, Gentofte, DK-2900 Copenhagen, Denmark. bisgaard@copsac.dk Received 20 November 2006; Revised 9 April 2007; Accepted 16 April DOI /ppul Published online 27 June 2007 in Wiley InterScience (

2 724 Bisgaard and Szefler conducted by experienced telephone fieldwork agencies based on a structured questionnaire with closed-ended questions (questionnaire available on-line). The interviews took place during April and May, pertaining to the previous 6 months (i.e., the winter months). No ethics approval was obtained for such population survey. Telephone Interview Mothers (or stepmothers) in identified households with at least one preschool child (aged 1 5 years) were interviewed using the following four questions regarding each child. Question 1: Has the child had repeated episodes (days) with troublesome coughing in the last 6 months? Question 2: Has the child had repeated episodes with troublesome noisy breathing (for example wheezing, whistling, crackling, bubbling sounds) in the last 6 months. Question 3: Has the child suffered from repeated episodes with troublesome breathlessness or shortness of breath in the last 6 months? Question 4: Has the child been given any medicines, pills, puffers or other medication for his/her repeated days of troublesome respiratory symptoms in the last 6 months? In case of an affirmative answer to one or more of the questions a full interview was conducted. In brief, this focused on symptom characteristics and frequency, impact of cough, wheeze or breathlessness on lifestyle, healthcare resource use, clinical diagnoses of the child and medication used. In addition, respondents were asked if the child had ever been given a specific doctor diagnosis of a lower respiratory illness. All interviews were conducted in the language of the respondent by experienced interviewers from a central telephone facility in each country using computer-assisted telephone interviewing. The questionnaire was developed in English, translated to the relevant languages and subsequently back translated to English to control for consistency. Results were summarized in frequency tables. Relative frequencies were compared using the Chi-square test. P-values less than 0.05 were considered statistically significant. No adjustments for multiple tests were applied. RESULTS Overall Population (N ¼ 9.490) A total of 9490 children aged 1 5 years (52% male) in 7251 households were identified and were screened for ABBREVIATION ICS, Inhaled corticosteroid. respiratory symptoms (Fig. 1). Overall, 3077 (32%) of the 9490 children reported recurrent days with cough, wheeze or breathlessness in the preceding 6 winter months. The prevalence varied from 29% in Northern Europe (Denmark 23%, UK 29%, and Germany 36%) to 48% in Southern Europe (Italy 45%, Spain 50%, and France 51%). The overall prevalence in the USAwas 27% with no clear geographical gradient. Gender effect was small with a prevalence of cough, wheeze or breathlessness of 34% in boys compared with 30% in girls. In girls there was a small peak at 3 years, but no age-dependence was seen in boys. Interview Population (N ¼ 2.700) In 2700 households with at least one child with recurrent days with cough, wheeze or breathlessness, the mother completed a full interview (see Fig. 1). Symptom Character Recurrent days with cough were reported by 87%, wheeze by 42%, breathlessness by 21%, and all three symptoms by 15% of children in this population. The symptom profiles for cough, wheeze or breathlessness appeared very similar: troublesome days of cough, wheeze or breathlessness occurred at least once a week in 23%, 26%, and 31% of children, respectively, and were present every day in 10%, 10%, and 13% of children, respectively; the duration of days of cough, wheeze or breathlessness was at least 1 week in 36%, 33%, and 25%, respectively; 38%, 45% and 54% of children with cough, wheeze or breathlessness, respectively, were affected by such symptoms in the absence of a cold; and days with cough, wheeze or breathlessness were unrelated to exercise in 88%, 90% and 82% of cases. Treatments were given for such symptoms in 84%, 86%, and 83% of children. Frequency of symptoms was categorized as intermittent (symptoms less than weekly) in 76% of the interviewed population, mild persistent (symptoms less than twice a week) in 10%, and moderate to severe persistent (twice weekly or more) in 14%. Taken together, 24% of the interview population (i.e., 8% of the overall population) suffered persistent symptoms during the previous 6 months despite current treatment (Table 1). Regional differences in symptom severity showed a larger symptom burden in Southern Europe with persistent symptoms in 30% of the interview population compared with 23% in USA and 19% in Northern Europe. Persistent symptoms were similar in boys (25%) and girls (23%) and with no clear age-dependence. Lifestyle Impact Fifty-eight percent of children had had their sleep disturbed by his/her cough, wheeze or breathlessness, in

3 Cough, Wheeze or Breathlessness in Young Children 725 Fig. 1. Flow of subjects interviewed in survey. 31% of cases at least once a week. The symptoms limited the child s normal activities in 33% of the population; 6% on at least a weekly basis. Thirty percent needed some form of medication before, during or after exercise because of their symptoms. Use of Healthcare Resources Primary care physician was seen by 85% of children because of their cough, wheeze or breathlessness, with 35% of children making three or more visits (Table 2). Outpatient clinics were used by 18% of children, while 16% and 12% of children, respectively, had required TABLE 1 Persistent (Weekly) Wheeze, Cough, and Breathlessness During Previous 6 Months Within Segments of the Interview Population (N ¼ 2700) Interview population N Persistent (weekly) symptoms Overall Regions USA Northern Europe Southern Europe Gender Boys Girls Age, years Doctor diagnosed asthma Yes No ICS treatment within recent 6 months Yes No emergency room care or overnight hospitalization at least once (Table 2). Diagnoses Twenty percent of the interview population had been diagnosed with asthma, 22% in USA, 26% in Northern Europe and 12% in Southern Europe. Medication (Table 3) The majority of children had received treatment for these respiratory symptoms in the previous 6 months, 67% for cough, 78% for wheeze and 83% for breathlessness (Table 3). Antibiotics and cough-medication were the most commonly prescribed with only small regional variation, although herbal-medications were widely used in Northern Europe, less so in Southern Europe and comparatively little use in USA. Prescription of inhaled b 2 -agonists was more uncommon in Southern Europe than in USA and Northern Europe. This was often for regular use in Northern Europe and more so than in Southern Europe and USA. Inhaled corticosteroid (ICS) use was much more common in Southern Europe compared with Northern Europe and USA, largely due to use of ICS for intermittent treatment in Southern Europe compared with Northern Europe and USA. Antihistamines were widely used in USA and Southern Europe and mostly for regular use, with little usage of antihistamines in Northern Europe. Oral corticosteroids were widely used in Southern Europe but to a lesser extent in USA and Northern Europe; this usage was mostly for regular treatment. Persistent symptoms were more prevalent in children on ICSs with 40% reporting symptoms at least weekly compared to 22% in children not using ICS (Table 1). Delivery device use for inhaled medications varied between regions. In the USA 25% of children taking an inhaled medicine used a pmdi þ spacer, while 81% used a

4 726 Bisgaard and Szefler TABLE 2 Healthcare Resource Utilization Associated With Recurrent Days With Wheeze, Cough and Breathlessness in Preschool Children Within the Previous 6 Months Health care resource utilization. Frequency during previous 6 months Overall USA North Europe South Europe Statistical Comparison of regions (Chi-square test) Visited primary care physician P < visits P < Attended an outpatient clinic P ¼ Visited an emergency room P < Hospitalized P < Interview Population (N ¼ 2700). nebulizer; in Northern Europe this ratio was 51%:55%, and in Southern Europe 34%:67%. DISCUSSION This survey showed that approximately one third of young children is affected by recurrent days troubled by cough, wheeze or breathlessness. The severity of symptoms captured in this survey was of significance causing most of the children to receive medication and to visit their family doctor, emergency department or being hospitalized in recent 6 months, as well as impact on the quality of life. There was a significant regional variation in prevalence, and use of asthma diagnosis and choice of medication. Together this survey documents the large unmet need represented by asthma-like symptoms in young children. Prevalence of asthma-related symptoms and diagnoses in preschool children has not been reported previously. The International Study of Asthma and Allergies in Childhood reported on the worldwide prevalence of selfreported asthma in school children, but did not study preschool children. Therefore there are no comparable data. 5 Asthma prevalence cannot be estimated from this survey. There is no international consensus on the criteria TABLE 3 Most Commonly Used Medications (Rescue, Intermittent, and Regular) Medication Overall USA N-Eur S-Eur Cough medication Antibiotics Inhaled b 2 -agonist, regular use Inhaled b 2 -agonist, intermittent use Herbal medication Inhaled corticosteroid, regular use Inhaled corticosteroid, intermittent use Anti-histamine, regular use Anti-histamine, intermittent use Oral corticosteroid LTRA Oral b 2 -agonist LTRA, leukotriene receptor antagonist. for the diagnosis of asthma in preschool children except for the most severe cases. Objective measures are rarely available for the diagnosis. The academic tradition defines asthma from a history of recurrent wheeze, but this is disconnected from clinical practice. Wheeze does not carry a specific meaning shared by lay people within or between cultures. Studies have shown that terms such as wheeze and difficulty in breathing have little validity when comparing clinical cases between parents but also between clinicians, and the conceptual understandings of wheeze for parents of children with reported wheeze are different from definitions used in epidemiology. 3,4 In clinical trials the composite symptom score such as symptom-free days are typically more sensitive than individual symptoms. 6,7 We therefore chose to interview mothers for the broader spectrum of airway symptoms wheeze, cough, and breathlessness emphasizing severity and recurrence of symptoms, lasting for days, and emphasizing symptoms from lower airways separate from symptoms from upper airways. The severity of the symptoms captured was of significance as reflected by most cases having attended family doctor or outpatient clinic or had been hospitalized in recent 6 months. The symptoms of cough, wheeze or breathlessness significantly impacted on the child s and caretaker s lifestyle, including limitations in exercise of the child and sleep disturbance of both the child and caretaker. Clearly the symptom description is biased from unreliable separation of lower and upper airway symptoms, and from different levels of concern depending on cultures. However, such uncertainties are no different from the history obtained in clinical practice. Therefore, our data represent the unspecific burden of recurrent asthma-like symptoms upon which doctors base their treatment, and represent a major disorder that burdens the lives of young children, is a major cause for hospitalization, medication use and other healthcare resource utilization, and is often considered and treated as asthma in clinical practice. Studies are needed to improve our ability to communicate the clinical symptoms reflecting early asthma allowing research to move beyond wheeze for diagnosis. This would allow more precise surveys into prevalence

5 Cough, Wheeze or Breathlessness in Young Children 727 and treatments but also risk factor analyses, and would impact on clinical trials as well. Overall, one-third (32%) of a sample of young children 1 5 years of age in USA and Europe had suffered asthmalike symptoms over the past 6 winter months. The majority had received medication for such symptoms, despite which the frequency of symptoms suggests that one-quarter had persistent symptoms (i.e., at least weekly symptoms). Importantly, this does not reflect the severity of the underlying disease as this symptom burden in on concurrent treatment, that is, it would be expected that the underlying disease burden is more severe. Children treated with regular ICS showed more severe symptoms (40% on ICS reporting symptoms at least weekly compared to 22% in children not using ICS). This not only suggests that children with more severe underlying disease are more often receiving regular ICS but also that there is heterogeneity of pathology causing persistent cough, wheeze or breathlessness in preschool children as the treatment outcome is clearly unsatisfactory in many cases. The survey follows on to previous surveys using similar methods but focusing on adults and school children. 8,9 It is a potential limitation of the findings from such studies that they are telephone-based and therefore households with no telephone were excluded. Such households are primarily those with low socioeconomic status, for whom the rate of lower respiratory symptoms among preschool children may be increased, 10 yet access to medical care may be reduced. Furthermore, the true prevalence is probably biased as families with symptomatic children were more likely to respond to the interview causing enrichment of symptomatology. Also, it should be emphasized that the questionnaire specified the previous winter months where symptoms are worse than the summer months. It is particular to the preschool child that the symptom history depends on second-hand description that is reliant on the caretaker s ability to observe and report intelligibly the symptoms presented by the child. Also, the child is often away from the primary caretaker for large parts of the day. Both factors are likely to cause a trend toward underestimating the true prevalence of recurrent days with cough, wheeze or breathlessness in young children. Regional variation of cough, wheeze or breathlessness was considerable, with rates of approximately 27% in most regions of the USA, 29% in Northern Europe, and 48% in Southern Europe. Asthma was diagnosed by a doctor in 20% of the interview population. Although Southern Europe had the highest prevalence rate of cough, wheeze or breathlessness of the three regions, it had a low rate of asthma diagnosis compared with Northern Europe and USA. Antibiotics, cough- and herbal- medications were the most commonly used treatments. Asthma and allergy treatments were used in the order: inhaled b 2 -agonists > ICS > oral anti-histamines > oral corticosteroids > leukotriene receptor antagonists > oral b 2 - agonists. Evaluation of medication use by region found a particularly high usage of regular inhaled b 2 -agonists in Northern Europe; high usage of short courses of ICS in Southern Europe; high usage of regular anti-histamine treatment in the USA and to some extent in Southern Europe, and a high usage of regular oral corticosteroid treatment in Southern Europe. A recent survey of a cohort biased toward South-Asian families in the UK showed usage of medication comparable to our findings. 11 Nebulizers were preferred over pmdi with spacer in the USA and Southern Europe, whereas the majority of children used a pmdi plus spacer in Northern Europe. In conclusion, recurrent days with troublesome cough, wheeze or breathlessness are a major cause of morbidity in preschool children, accounting for significant lifestyle impact, and use of healthcare resources despite current treatment, and represent a very large group of poorly treated patients. The considerable regional variation in the population symptom burden and doctors diagnosis of asthma together with significant differences in prescribed medications shows a striking lack of international consensus on diagnosis and treatment in this age group. Importantly, this uncontrolled morbidity highlights a significant unmet clinical need and begs more resources being directed to the understanding of this heterogeneous disorder in preschool children to improve our diagnostic and therapeutic means. REFERENCES 1. Kocevar VS, Bisgaard H, Jonsson L, Valovirta E, Kristensen F, Yin DD, Thomas J. Variations in pediatric asthma hospitalization rates and costs between and within Nordic countries. Chest 2004;125: Martinez FD, Wright AL, Taussig LM, Holberg CJ, Halonen M, Morgan WJ. Asthma and wheezing in the first six years of life. The Group Health Medical Associates. N Engl J Med 1995;332: Cane RS, Ranganathan SC, McKenzie SA. What do parents of wheezy children understand by wheeze? Arch Dis Child 2000; 82: Cane RS, McKenzie SA. Parents interpretations of children s respiratory symptoms on video. Arch Dis Child 2001;84: Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. 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