Raised immunoglobulin E and idiopathic bronchiectasis
Article Outline
Summary
We describe a series of 4 subjects with markedly raised immunoglobulin E levels in association with idiopathic bronchiectasis. This has not been described previously and appears to be a distinct entity from other conditions such as allergic bronchopulmonary aspergillosis.
Keywords: Bronchiectasis, Immunoglobulin, ABPA
Introduction
An elevated immunoglobulin E (IgE) level is associated with bronchiectasis in the context of allergic bronchopulmonary aspergillosis (ABPA). We describe a series of 4 subjects who had idiopathic bronchiectasis with markedly raised IgE but without evidence of ABPA.
Case report
A series of 4 patients was assessed at Monash Medical Centre (MMC) for bronchiectasis. The group comprised 2 male and 2 female subjects with a mean age of 44 years. All patients had a clinical assessment performed by a respiratory physician (PK). Subjects were all living independently, did not have significant other medical conditions and were not taking immunosuppressive medication. One subject had had tuberculosis previously that was treated when he was 17.
All subjects had a chronic productive cough (range 1–18 years). Three of the 4 subjects described significant chest infections in childhood that interfered with schooling. One subject had been diagnosed by a respiratory physician as having asthma. Three of the subjects had symptoms of rhinosinusitis. There was no family history of significant chest infections or other features to suggest cystic fibrosis.
Subjects had a high resolution CT scan performed to diagnose bronchiectasis. All subjects had multi-lobar disease (mean number of lobes involved 3, range 2–4). One subject had predominantly central bronchiectasis. Spirometry of the group demonstrated mild airway obstruction (mean FEV1 of 76%, range 58–111%). No subject had significant airway reversibility to salbutamol inhalation. Screening for underlying bronchiectasis was performed including; full blood examination, immunoglobulins, neutrophil function, lymphocyte subsets and function, alpha-1 antitrypsin levels, cystic fibrosis mutation analysis and ABPA. All 4 subjects had markedly elevated serum IgE levels that were more than 3 times above the normal range (all subjects were tested at least twice and results averaged). Clinical history and screening revealed no underlying cause for bronchiectasis and all subjects were classified as having idiopathic disease. Results of screening for ABPA are shown in Table 1. Subjects all had a bronchoscopy to assess airway function; 1 subject had a raised eosinophil count and positive cultures were obtained in 2 subjects, both isolates of Haemophilus influenzae.
Table 1.
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | |
|---|---|---|---|---|
| Mean IgE level (IU/ml) | 3512 | 2130 | 1821 | 752 |
| Age (years) | 28 | 45 | 55 | 47 |
| Diagnosis of asthma | No | No | No | Yes |
| Blood eosinophil count (×109/L) | 0.3 | 0.1 | 0.1 | 0.3 |
| Central bronchiectasis | No | No | Yes | No |
| Skin test reaction to Aspergillus | No | No | No | No |
| Aspergillus precipitins | No | No | No | No |
| Isolation of Aspergillus from bronchoscopy/sputum | No | No | No | No |
Subjects were followed up regularly at MMC and treated with multiple courses of antibiotics and prednisolone. Three of the subjects had significant benefit from this treatment but still had ongoing symptoms and elevated IgE levels. The other subject developed an abscess which required thoracotomy and drainage; histology demonstrated bronchiectasis with multiple organizing abscesses and infiltration with macrophages, plasma cells and lymphoid follicles (Fig. 1). H. influenzae was grown from the lung tissue (no growth from previous bronchoscopy).
Figure 1
CT scan of a patient demonstrating; (A) extensive bronchiectasis in right upper lobe and (B) loculated collection in left lower lobe which was subsequently resected.
Discussion
Bronchiectasis is associated with a large number of different aetiological factors, although commonly the condition is idiopathic.1, 2 A classical condition associated with bronchiectasis is allergic bronchopulmonary aspergillosis.
ABPA most commonly occurs in the context of asthma or cystic fibrosis although some patients seem to have neither condition.3 The minimal diagnostic criteria in asthma have been described as being; (1) central bronchiectasis (2), immediate cutaneous reactivity to Aspergillus species (3) serum IgE
>417IU/L and (4) elevated IgG or IgE-A. fumigatus.4 In cystic fibrosis minimal diagnostic criteria have been listed as being; (1) acute/subacute deterioration not attributable to another aetiology (2), serum IgE>500IU/ml (3), immediate cutaneous reactivity to Aspergillus species and (4) precipitins/IgG to A. fumigatus or new X-ray changes.5 As only 1 subject in this cohort had a diagnosis of asthma with no subject having a diagnosis of cystic fibrosis or having skin reactivity to Aspergillus or precipitins these subjects would not be classified as having ABPA.
Another condition characterized by elevated IgE levels and respiratory infection is the Hyper-IgE syndrome (or Job syndrome). The classical features of this condition are elevated IgE, recurrent staphylococcal skin abscesses and pneumonia with pneumatocele formation.6 Other major features include eczema and characteristic skeletal abnormalities7 and cerebral symptoms in the rarer recessive form.8 This cohort of 4 subjects did not have the additional features that would suggest a diagnosis of Hyper-IgE syndrome.
Previous studies have reported a high incidence of broncho-reactivity in bronchiectasis (range of 24–69%).2, 9, 10 Whether this represents asthma or is only the response of inflamed and infected airways is not known. Elevated IgE levels are associated with a lack of type 1 T helper (Th) lymphocyte activity and shift to Th2 responses and this has been demonstrated in both ABPA4, 5 and the Hyper-IgE syndrome.6 This response is thought to explain the recurrent infections that occur in these conditions. The authors have also described similar bias in lymphocyte responses to nontypeable H. influenzae in idiopathic bronchiectasis.11, 12
The suggestion from this cohort of 4 patients is that an elevated IgE level may be associated with increased susceptibility to bronchial infection with pathogens other than Aspergillus that results in bronchiectasis.
Conflict of interest statement
The authors have no conflict of interest in this work.
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PII: S1755-0017(08)00065-1
doi:10.1016/j.rmedc.2008.07.014
© 2008 Elsevier Ltd. All rights reserved.
