Sinusitis is a common occurrence in children with asthma. In fact, rhinosinusitis, based on suggestive upper airway symptoms and supportive radiographic changes, is present in nearly 30% to 50% of pediatric patients with asthma.1"3 Eosinophils are an important common histologic factor in patients with chronic sinusitis and asthma. Clinical studies demonstrate that aggressive medical treatment, surgical treatment, or both of sinusitis can significantly improve lower airway disease in children with asthma. These observations suggest that sinusitis may play an important role in initiating or exacerbating childhood asthma. This has important implications for the clinician evaluating and treating a child with bronchial hyperresponsiveness.
This article reviews the historical evidence of the coexistence of sinusitis and asthma in children, underscores the importance of the eosinophil as an airway mflammatory cell, explores the evidence that medical or surgical treatment of sinusitis can improve asthma, and makes suggestions for the clinical management of persistent childhood asthma and associated chronic or recurrent sinusitis. Speculations about potential mechanisms by which rhinitis and sinusitis could have an impact on asthma are described in the article by Lieberman in this issue.
COEXISTENCE OF SINUSITIS AND ASTHMA
Nearly 2,000 years ago, Galen first noted that sinusitis could cause asthma. He felt that this occurred because secretions dripped from the skull directly into the lungs. Accordingly, he introduced nasal irrigation and purging as treatment for sinusitis and asthma. This became a routine approach until 1650, when anatomists were unable to demonstrate any direct connection between the skull and the lungs.
In the 1930s, Chobot1 found that the incidence of sinusitis (based on clinical symptoms) was as high as 70% in children with asthma. More recently, Rachelefsky et al.2 and Zimmerman et al.3 demonstrated that 21% to 31% of children with asthma have significantly abnormal findings on sinus radiographs (ie, mucosal thickening > 5 mm, air-fluid levels, or opacification of one or more sinuses). Independently, Kovatch et al.4 studied asymptomatic (normal) children and found only a 5% to 6% incidence of significant radiographic changes. Children younger than 1 year were a notable exception, with a 36% incidence. However, radiographic opacification is not specific in children younger than 1 year because they have not fully aerated their maxillary sinuses. In other words, children with asthma are 4 to 5 times more likely to demonstrate abnormal findings on sinus radiographs than are their healthy counterparts without asthma.
EOSINOPHILS IN CHRONIC RHINOSINUSITIS AND ASTHMA
In 1929, Hansel5 reported a remarkable similarity between the histologic changes in chronic sinusitis and asthma. Both diseases are characterized by eosinophilic tissue infiltration, glandular hyperplasia, and stromal edema.
Harlin et al.6 examined the role of eosinophils as a causative factor for chronic sinusitis. They reviewed surgical sinus samples from 26 adolescents and adults for the presence of eosinophils or major basic protein (MBP), a significant eosinophil granular protein. Sinus tissue from all 13 patients with asthma and 6 of 7 patients with allergic rhinitis showed significant eosinophils and MBP. None of the 6 patients without asthma or allergic rhinitis showed tissue eosinophilia, and only 1 had detectable levels of MBP.
The effect of MBP on sinus mucosa in vitro was explored by Hisamatsu et al.7 MBP at concentrations likely to be present in vivo caused epithelial damage and ciliary dysmotility. These researchers argued for a causative role of the eosinophil in acute bacterial sinusitis, nasal polyposis, and both nasal and bronchial hyperresponsiveness.
EFFECT OF MEDICAL TREATMENT OF SINUSITIS ON ASTHMA
Several groups have examined the effect of aggressive medical treatment of sinusitis in children with asthma. In 1983, Cummings et al.8 compared treatment with antibiotics, nasal corticosteroids, and oral decongestants versus placebo in children with asthma who had opacified or markedly thickened maxillary sinuses. Only the active treatment group showed reduced asthma symptoms and less need for bronchodilator or oral corticosteroid therapy. However, there was no significant change in either group in measures of pulmonary function or bronchial responsiveness.
In 1984, Rachelefsky et al.9 studied 48 children with a 3-month or more history of sinusitis and wheezing. Treatment included antibiotics and, in some cases, antral lavage. Nearly 80% (38 of 48) were able to discontinue bronchodilators and more than half of the children returned to normal pulmonary function.
A smaller study by Friedman et al.10 assessed the effect of antibiotics alone in the treatment of an acute exacerbation of sinusitis and asthma. Nearly all (7 of 8) children showed dramatic improvement in asthma symptoms. The airways response to a bronchodilator was twice as great after treatment, although baseline spirometry was unchanged.
Further evidence that treating eosinophilic rhinitis can enhance lower airway disease was noted by Corren et al.11 This group showed that nasal allergen challenge in patients with seasonal allergic rhinitis can induce increases in bronchial responsiveness for up to 4 hours. A subsequent study demonstrated that this effect could be prevented by pretreatment with nasal corticosteroids.12
EFFECT OF SURGICAL TREATMENT OF SINUSITIS ON ASTHMA
In 1984, Werth13 reported a marked improvement in all airway symptoms after sinus surgery in 20 of 22 children with refractory sinusitis and asthma. Typically, surgical intervention included at least antral lavage and adenoidectomy.
These results were in concordance with adult studies by Davison14 in the 1960s and Slavin15 in 1982. In these studies, nearly all patients showed significant improvement in asthma after surgical intervention for chronic sinusitis.
The realization that sinusitis and asthma frequently coexist and that sinusitis can exacerbate asthma has important implications for the evaluation of chronic childhood asthma. The child with persistent asthma and a pattern of recurrent or chronic sinusitis deserves special consideration.
Evaluation of Chronic Childhood Asthma
The evaluation of a child with chronic asthma should consider the possibility of underlying allergic rhinitis, sinusitis, gastroesophageal reflux disease, or all three.16 At any point in time, the chronic picture may be intensified by various acute triggers (eg, viral upper respiratory infection, cold air, or exercise).
Because nearly all children older than 5 years with asthma are atopic, initial evaluation should focus on the role of allergy as a source of airway inflammation. As such, allergic rhinitis can induce chronic rhinorrhea, nasal obstruction, sinus ostial obstruction, nasal hyperresponsiveness, and bronchial hyperresponsiveness. Determination of allergen-specific IgE provides the basis for aggressive environmental control, appropriate pharmacotherapy, and, occasionally, immunotherapy.
Sinusitis should be suspected on the basis of a clinical history of symptoms of upper respiratory infection persisting beyond 7 to 10 days. Prominent symptoms typically include nasal congestion and nocturnal cough, often to the point of vomiting. Often there has been a "rollercoaster" history with associated asthma: stability while taking oral steroids, but then gradual deterioration during 1 to 2 weeks when therapy is "stepped down." In addition to a careful history and directed examination, nasal cytology and radiographic imaging can be useful, clarifying the nature of upper airway inflammation and the extent of mucosal disease.
Gastroesophageal reflux disease is suggested by a history of chest discomfort hours after meals, especially when symptoms are relieved by eating or the use of antacids or H2-antagonists. This is particularly a consideration with "cough-variant" asthma, where cough without wheeze is a sign of bronchial hyperresponsiveness. In fact, moderate or severe gastroesophageal reflux disease may even increase the risk for sinusitis, possibly through neural reflex pathways, direct airway irritation, or both.
Management of Persistent Childhood Asthma and Associated Chronic or Recurrent Sinusitis
Given the association of allergic rhinitis with asthma and sinusitis, successful management of chronic childhood asthma must adequately address upper airway allergy. At the same time, sinusitis should be suspected in any child with asthma that is difficult to manage. In this setting, aggressive treatment for sinusitis is the best way to achieve persistent improvement in asthma.
Management of Allergic Rhinitis
Environmental controls should focus on significant indoor allergens (eg, dust mites, cockroaches, animals, and indoor molds), with particular emphasis on the child's bedroom. The primary goal of pharmacotherapy for allergic rhinitis is reduction of airway inflammation as the source for most nasal symptoms, sinus ostial obstruction, nasal hyperresponsiveness, and bronchial hyperresponsiveness.17
From clinical experience, a "stepwise" approach to allergic rhinitis similar to the asthma guidelines seems prudent. For mild allergic rhinitis, a nasal corticosteroid might be needed only during periods of "extra" inflammation (eg, a pollen season or an upper respiratory infection). For more moderate or severe disease, a routine nasal corticosteroid should be instituted with increased dosage during upper respiratory infections. Once the upper respiratory infection has resolved, therapy can be stepped down. Immunotherapy becomes a consideration when chronic rhinitis, sinusitis, asthma, or all three continue to affect quality of life despite aggressive environmental control and pharmacotherapy.
Management of Acute Sinusitis
Acute bacterial sinusitis is a clinical diagnosis based largely on the persistence of symptoms of upper respiratory infection beyond 7 to 10 days, including fatigue, purulent rhinorrhea, nasal congestion, and cough.18 Some patients may also complain of fever, headache, sore throat, or halitosis. The diagnosis is supported by the presence of neutrophilic rhinitis and radiographs demonstrating mucosal thickening of at least 50% of the affected sinus, air-fluid level, or opacification. Appropriate therapy includes 2 to 4 weeks of antibiotics and adjunctive medication to enhance drainage of infected secretions from the sinuses.
The choice of antibiotic should consider the possibility of resistant Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.19 With this in mind, the best choice for monotherapy is amoxicillin or amoxicillin-clavulanate (plus additional amoxicillin if resistant S. pneumoniae is a concern). Cefuroxime or Cefpodoxime may also be used, and azithromycin, clarithromycin, cefdinir, cefprozil, and loracarbef have a reasonable spectrum of coverage. With persistent infection, an alternative approach includes using two agents with enhanced total coverage (eg, clindamycin and Ceftibuten).
Adjunctive therapy may include nasal or even oral corticosteroids20 in sinusitis with marked mucosal thickening. Other medications that may be useful include nasal or oral decongestants (particularly in the first few days of therapy) or mucolytics (eg, guaifenesin).
Management of Recurrent or Chronic Sinusitis
A pattern of recurrent acute bacterial sinusitis or chronic sinusitis raises concern about underlying allergic rhinitis, anatomic problems, or immunodeficiency. A first step is to reinforce environmental controls and consider "stepping up" pharmacologic therapy for allergic rhinitis. Sinus anatomy is best assessed with a full coronal sinus computed tomography scan - 3-mm cuts throughout the sinuses and additional 1-mm cuts through the osteomeatal complex (involving the anterior ethmoid, middle turbinate, and maxillary sinus ostial areas).21 Baseline assessment of the immune system includes quantitative immunoglobulin measurement. This should be assessed in any child with associated recurrent otitis media or pneumonitis or if surgical intervention for sinusitis has been planned. A secondary qualitative test (eg, response to pneumococcal immunization) should be performed in the child with a poor clinical course despite prior sinus surgery.22
Sinusitis occurs in 30% to 50% of children with asthma. In fact, in children with chronic disease, eosinophils represent a common histologic component of both diseases. Aggressive medical or surgical treatment of sinusitis can significantly improve both upper and lower airway symptoms in these patients. The management of persistent childhood asthma and associated chronic or recurrent sinusitis should focus on reducing the impact of allergy on the airway with a combination of environmental control, nasal corticosteroids, and, occasionally, immunomodulation.
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3. Zimmerman B, Stringer D, Feanny S, et al. Prevalence of abnormalities found by sinus x-rays in childhood asthma: lack of relation to severity of asthma. J Allergy Clin Immunol. 1987;80:268-273.
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22. Joint Task Force on Practice Parameters. Parameters for the diagnosis and management of sinusitis: congenital or acquired immunodeficiency. J Allergy Clin Immunol. 1998;102:130-131.