PISA, ITALY—Some asthmatic children exhibit structural lung changes similar to those seen in emphysema. Italian researchers recently found that 31% of the children in their study had low-density areas on high-resolution computed tomography (HRCT) scans, despite three months of treatment.[1]

What causes these low-density areas? In adult smokers, such changes are due to enlargement of air spaces near damaged tissue when alveolar walls are destroyed by emphysema. In asthmatic nonsmokers, such findings could be caused by peribronchial fibrosis and subsequent air trapping. This is the first time that airway changes resulting in low-density areas have been shown to occur in children.

LUNG FUNCTION TESTING AND HRCT

Thirty-two children ages 8 to 14 were enrolled in the study led by Massimo Pifferi, MD, from the University of Pisa. All children met the American Thoracic Society criteria for diagnosis of chronic persistent asthma. Patients with atopic dermatitis were excluded to avoid difficulty in interpreting eosinophil counts and eosinophil cationic protein (ECP) results.

Pulmonary function tests, peripheral eosinophil count, total serum immunoglobulin E levels, and serum ECP values were taken both at baseline and after three months of treatment with twice-daily salmeterol (50 µg) and fluticasone propionate (250 µg).

A carefully designed HRCT study was performed only at the end of the three-month treatment period to avoid exposing pediatric patients twice to radiation. After the scout view acquisition, two inspiratory and expiratory slices were obtained and subsequently evaluated using the following scoring system: 0 = no hyperlucent area in lung parenchyma, 1 = poorly defined low-density areas, 2 = well-defined low-density areas (see Figure 1).

Figure 1 HRCT Scoring System
A C E	B D F
Score 0: (A) inspiratory, (B) expiratory; Score 1: (C) inspiratory, (D) expiratory; Score 2: (E) inspiratory, (F) expiratory. HRCT = high-resolution computed tomography. Source: Reprinted with permission. J Pediatrics. 2002.

Of the 32 patients, 22 had a score of 0 on HRCT, five had a score of 1, and five had a score of 2. Thus, HRCT scans from 10 (31%) patients showed low lung density areas.

In these patients, the posttreatment decrease in eosinophil count failed to reach significance. In addition, neither mean forced expiratory flow during the middle half of forced vital capacity (FEF25-75) nor residual volume (RV) showed a significant change after treatment. In patients without low-density areas, however, treatment achieved significant reductions in eosinophil count and RV values, as well as an increase in FEF25-75.

The investigators were able to show a significant association between the persistence of a high RV value and a positive HRCT scan (defined as a score of 1 or 2).

The authors admit certain limitations to the study. First, no baseline HRCT scans were performed at enrollment for comparison. Second, they did not try to detect bronchiectasis because obtaining the thin slices necessary for evaluation would have subjected the pediatric patients to excessive radiation.

Despite these limits, this study demonstrates that chronic asthma may cause parenchymal changes at an early age. Although the cause of these low-density areas cannot be definitively stated, the authors suggest peribronchial fibrosis or vascular remodeling rather than eosinophilic inflammation.

The relationship between asthma and emphysema-like changes requires further study, especially with regard to the decline in lung function in patients with low-density areas on HRCT or persistently high RV values. In addition, treatment options for these patients need to be evaluated.

—Lisa Pallatroni