Evaluation and management of pulmonary disease in ataxia-telangiectasia

Abstract

Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ATM gene, resulting in faulty repair of breakages in double-stranded DNA. The clinical phenotype is complex and is characterized by neurologic abnormalities, immunodeficiencies, susceptibility to malignancies, recurrent sinopulmonary infections, and cutaneous abnormalities. Lung disease is common in patients with A-T and often progresses with age and neurological decline. Diseases of the respiratory system cause significant morbidity and are a frequent cause of death in the A-T population. Lung disease in this population is thought to exhibit features of one or more of the following phenotypes: recurrent sinopulmonary infections with bronchiectasis, interstitial lung disease, and lung disease associated with neurological abnormalities. Here, we review available evidence and present expert opinion on the diagnosis, evaluation, and management of lung disease in A-T, as discussed in a recent multidisciplinary workshop. Although more data are emerging on this unique population, many recommendations are made based on similarities to other more well-studied diseases. Gaps in current knowledge and areas for future research in the field of pulmonary disease in A-T are also outlined.

Figure 1

CT image of 17 year old female with A-T and history of recurrent pneumonias, dysphagia and bronchiectasis. This single CT image demonstrates right middle lobe bronchiectasis and bronchial wall thickening, peripheral tree in bud opacities and scattered areas of ground glass opacity.

Figure 2

Lung biopsy of a 19 year old male with A-T and chronic pulmonary symptoms. A. Lung biopsy showed a diffuse interstitial process characteristic of early organizing diffuse alveolar damage with mild alveolar wall fibrosis and lobular remodeling, a mild interstitial infiltrate of predominantly lymphocytes, and patchy alveolar epithelial hyperplasia with scattered atypical cells having large hyperchromatic nuclei (arrows). B. In other regions there were more superimposed acute changes with hyaline membrane formation and mild mixed inflammation.

Figure 3

CT image of 14 year old boy with respiratory failure following chemotherapy for lymphoma. This CT image, through the upper lungs demonstrates mosaic attenuation with bilateral geographic areas of predominantly ground glass opacity. Several dilated bronchi are seen in the right upper lobe. Note that this image shows some blurring from motion, to decrease radiation exposure, images that are diagnostic but not ideal should not be repeated in people with A-T.

Figure 4

Diagram of set-up for performing PFTs on patient with A-T. Panel A illustrates the use of both hands to stabilize the patient's cheeks during the forced expiratory maneuver. Panel B shows the use of one hand to stabilize the cheeks and mandible while using the opposite hand to stabilize the head.