Chapter 48: Allergic Bronchopulmonary Aspergillosis (Mycosis) and Severe Asthma with Fungal Sensitivity

Introduction

Allergic bronchopulmonary aspergillosis (ABPA) is an idiopathic inflammatory disease of the lung, characterized by an allergic inflammatory response to colonization of the airways by Aspergillus fumigatus or other fungi. The entity was first described in 1952 by Hinson et al., and then again in 1967, when Scadding recognized an association between the disease and proximal bronchiectasis in areas previously affected by infiltrates (predominantly in the upper lobes).^1,2 The first adult case of ABPA was reported in the United States in 1968.³ Although most cases entail hypersensitivity to Aspergillus spp. (especially A. fumigatus), the finding of a virtually identical clinical syndrome associated with immune sensitivity to Candida albicans (most commonly), Helminthosporium, Alternaria, Curvularia lunata, Drechslera hawaiiensis, Stemphylium languinosum, Saccharomyces cerevisiae, or Pseudallescheria boydii has led some to use the term allergic bronchopulmonary mycosis to describe the syndrome.⁴ However, since the predominant causative organism is A. fumigatus and the commercially available laboratory testing is for this organism, ABPA is primarily designated as the diagnosis. In addition, a new entity has been recently recognized that appears to be on the continuum between fungal allergy, at one end, and ABPA at the other: severe asthma with fungal sensitivity (SAFS).⁵

The precise prevalence of ABPA is unknown, in part due to variability in diagnostic criteria used in various studies, the lack of distinction between ABPA and mold-sensitive asthma, and delays in the diagnosis of patients with long-standing disease; however, it is clear that ABPA is a relatively common entity. Estimates are that true ABPA complicates approximately 7% to 14% of cases of chronic steroid–dependent asthma and approximately 7% to 15% of cases of cystic fibrosis (CF).

Most cases of ABPA are recognized in the third to fifth decade of life, but they may present during childhood. In some patients, it is likely that ABPA starts early in life and continues, unrecognized, until adulthood. Interestingly, familial cases have been reported, suggesting that genetic factors underlie development of ABPA.^6,7 The spectrum of disease is broad. Patients may be asymptomatic, have mild-to-moderate asthma, or have severe and debilitating disease, leading to lung transplantation. However, if recognized early and managed aggressively, ABPA is treatable and may remit indefinitely; progressive lung damage can be avoided.

For the purposes of this discussion, the focus is on ABPA. However, clinicians should be cognizant that diagnostic testing for other fungi needs to be pursued when organisms other than Aspergillus spp. are suspected. In addition, the newly defined form of asthma noted previously, SAFS, is discussed and differentiated from ABPA.

Pathogenesis

Although the pathogenesis of ABPA is poorly understood, it is believed to be the result of an exaggerated immunologic reaction to chronic airway colonization by Aspergillus (or other relevant fungal) species.⁸ Aspergillus spp. are globally ubiquitous, thermotolerant fungi that reside in decaying organic matter ...