Severe intermittent wheezing in preschool children: A distinct phenotype

Department of Pediatrics, Washington University in St. Louis, San Luis, Missouri, United States
Journal of Allergy and Clinical Immunology (Impact Factor: 11.25). 03/2007; 119(3):604-10. DOI: 10.1016/j.jaci.2006.12.607
Source: PubMed

ABSTRACT Young children with wheezing predominantly with respiratory tract illnesses experience severe exacerbations separated by extended periods of wellness and may be described as having "severe intermittent wheezing," a diagnostic category not currently recognized in national guidelines.
We sought to characterize a cohort of children with recurrent severe wheezing.
A total of 238 children 12 to 59 months enrolled in the Acute Intervention Management Strategies trial were characterized through comprehensive allergy, asthma, environmental, and quality of life assessments.
Asthma symptoms over the period of the preceding year occurred at frequencies consistent with intermittent asthma, as 94.5% of children experienced activity limitation < or = 2 times per month. However, frequent severe exacerbations were common, because 71% experienced > or = 4 wheezing episodes over the period of the preceding year, 95% made at least 1 primary care visit, 52% missed school or daycare, 40% made an emergency department visit, and 8% were hospitalized for wheezing illnesses. Atopic features were common, including eczema (37%), aeroallergen sensitization (46.8%), and positive asthma predictive index (59.7%). Oral corticosteroid use in the previous year (59.7% of the cohort) identified a subgroup with more severe disease documented by a higher incidence of urgent care visits (P = .0048), hospitalizations (P = .0061), aeroallergen sensitization (P = .047), and positive asthma predictive indices (P = .007).
Among preschool children enrolled in the Acute Intervention Management Strategies trial, a subgroup was identified with severe intermittent wheezing characterized by atopic features and substantial illness-related symptom burden despite prolonged periods of wellness.
Preschool children with recurrent severe wheezing episodes experience significant illness-related morbidity and exhibit features of atopic predisposition.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Toll-like receptors (TLR) belong to a large family of pattern recognition receptors known as the ancient 'gatekeepers' of the immune system. TLRs are located at the first line of defense against invading pathogens as well as aeroallergens, making them interesting targets to modulate the natural history of respiratory allergy. Agonists of TLRs have been widely employed in therapeutic or prophylactic preparations useful for asthma/allergic rhinitis (AR) patients. MPL® (a TLR4 agonist) and the CpG oligodeoxynucleotide of 1018 ISS, a TLR9 agonist, show strong immunogenicity effects that make them appropriate adjuvants for allergy vaccines. Targeting the TLRs can enhance the efficacy of specific allergen immunotherapy, currently the only available 'curative' treatment for respiratory allergies. In addition, intranasal administration of AZD8848 (a TLR7 agonist) and VTX-1463 (a TLR8 agonist) as stand-alone therapeutics have revealed efficacy in the relief of the symptoms of AR patients. No anaphylaxis has been so far reported with such compounds targeting TLRs, with the most common adverse effects being transient and local irritation (e.g. redness, swelling and pruritus). Many other compounds that target TLRs have been found to suppress airway inflammation, eosinophilia and airway hyper-responsiveness in various animal models of allergic inflammation. Indeed, in the future a wide variability of TLR agonists and even antagonists that exhibit anti-asthma/AR effects are likely to emerge. © 2014 S. Karger AG, Basel.
    International Archives of Allergy and Immunology 05/2014; 164(1):46-63. DOI:10.1159/000362553 · 2.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Guidelines recommend regular assessment of asthma control. The Childhood Asthma Control Test (C-ACT) is a clinically validated tool.AimTo evaluate asthma control according to GINA2006, NAEPP, pediatrician's assessment (PA), and C-ACT in asthmatic children visiting their ambulatory pediatrician or tertiary care pediatric pulmonologist.Methods Demographic data, treatment, and number of severe exacerbations during the previous year were collected. Control was assessed using (i) strict GINA 2006 criteria, (ii) GINA without taking into account the exacerbation item, (iii) NAEPP criteria, and (iv) PA. Children and parents filled out the C-ACT.ResultsFive hundred and twenty-five children completed the survey (mean age: 7.7 years; 28% ≤ 6 years). 78% had a controller treatment. 58% reported ≥ 1 severe exacerbation. C-ACT was ≤ 19 in 29.5%. Control was not achieved in 76.5%, 55%, 40%, and 34% according to GINA 2006 guidelines, NAEPP guidelines, GINA 2006 without exacerbation criteria, and PA, respectively. C-ACT was significantly lower in children ≤ 6 years old (P = 0.002) or with severe exacerbations (P < 0.0001). According to PA, 89% of patients with a C-ACT > 21 were controlled and 85% of patients with a C-ACT < 17 not controlled.Conclusion We observed discrepancies between the different tools applied to assess asthma control in children, and the impact of age and exacerbations. Cutoff point of 19 of C-ACT was not associated with the best performance compared to PA. Assessment of control should take into account symptoms and lung function as suggested by the latest GINA guidelines as well as exacerbation over a long period.
    Allergy 04/2014; DOI:10.1111/all.12402 · 6.00 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Asthma is a chronic inflammatory disease of the lower airway that is commonly encountered by the otolaryngologist. This article provides information on how to recognize patients with asthma and discuss issues related to diagnosis, treatment, and continued management within the context of current guidelines. MethodsA literature review was conducted and relevant sources are referenced concerning the epidemiology of asthma, the pathophysiology of asthma, diagnostic strategies, treatment options, and continued management. ResultsAsthma is a common condition worldwide and is often associated with other atopic diseases such as allergic rhinitis and eczema, though other genetic and environmental factors appear to be important as well. The lower airway and upper airways share similar histology, as well as patterns of inflammation in response to environmental triggers. The diagnosis of asthma involves a careful history and a complete physical exam, including auscultation of the lungs and pulmonary function testing. Pharmacotherapy represents the primary method of treating asthma, though current evidence supports a positive role for antigen-specific immunotherapy for both prevention and treatment. Guidelines are available that can assist the otolaryngologist in classifying the severity of asthma, determining the level of control and recommending modifications in the treatment plan. Conclusion As airway specialists, otolaryngologists are in a unique position to recognize and manage asthma in their patients, particularly those with allergic disease. Maintaining a high index of suspicion and understanding the key elements of diagnosis and treatment are extremely important in order to achieve this goal. (C) 2014 ARS-AAOA, LLC.
    International Forum of Allergy and Rhinology 09/2014; 4 Suppl 2(S2):S70-3. DOI:10.1002/alr.21386 · 2.37 Impact Factor