THE ASSOCIATION OF ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS AND CYSTIC FIBROSIS

Abstract

As has been discussed in other articles in this issue, allergic bronchopulmonary aspergillosis (ABPA) is a complication of asthma that may be more common than initially expected; however, it is a syndrome that occurs with variable frequency throughout the United States. In fact, some clinicians believe they have never seen a case, whereas in other parts of the United States a fairly large number of such cases are diagnosed and treated. Cystic fibrosis (CF) is the most common lethal genetic disease in the white population, with a prevalence of one in 2500 births. This disease is autosomal recessive, with the CF gene localized on the long arm of chromosome 7. CF has been associated with a deletion at position 508. The CF gene gives rise to a protein product called the cystic fibrosis transmembrane regulator protein (CFTR), which is related to a class of proteins that is involved in the transport of substances across cell membranes. An abnormal protein may interfere with chloride transport or may interfere with activation of transport mechanisms by protein kinases. The basic abnormality in CF is abnormal exocrine gland function, which is due to defective transport mechanisms that lead to the production of hyperviscous secretions.2 These hyperviscous secretions in the bronchial tree can become inspissated, and bacterial infections can occur with subsequent development of bronchiectasis and progressive pulmonary destruction from chronic and recurrent inflammation. In 1976, Mitchell-Heggs et al reported an association between CF and ABPA for the first time.13 Since that time, other investigators have reported that ABPA can occur in as many as 11% of patients with CF. This statistic may be an under-estimation because the lung disease in patients with CF may obscure some of the pulmonary findings considered typical of ABPA. However, distinguishing ABPA from other infectious complications in CF is crucial for proper treatment because untreated ABPA causes long-standing pulmonary inflammation, bronchiectasis, and fibrosis itself.1, 6, 12, 13, 17 On the other hand, when one small CF population was systemically examined for ABPA, only 1 of 53 patients was found to have ABPA.1 Aspergillus is a species of fungi that are ubiquitous throughout the environment and are tolerant to varied environmental conditions. These fungi are commonly cultured in surveys of homes as well as outdoors. Although several species of Aspergillus have been found to cause disease in humans, Aspergillus fumigatus is the most common. Studies determining the atmospheric spread of A. fumigatus spores indicate a worldwide distribution. Of interest is that there are similar levels reported in both North America and the United Kingdom. A. fumigatus grows at temperatures between 15°C and 53° C. Major antigenic glycoproteins that appear under different growth conditions have been identified.2, 8 The classical diagnostic criteria for the diagnosis of ABPA have already been reviewed by Patterson and Varkey (see their articles elsewhere in this issue). The applicability of these criteria to all cases of patients who may have both CF and ABPA has been put in question. Hutcheson et al have described a cohort of 79 patients where variable responses to A. fumigatus were seen over a period of time.7 This data shows the pitfall of basing the diagnosis of ABPA in CF patients solely on the basis of serology and skin test results.