Bronchial asthma is a clinical syndrome characterized by reversibility of airway obstruction which is caused by increased airway hyper-responsiveness to various stimuli but improved by therapy¹⁾. Over last several decades, bronchial asthma has been thought to be a completely reversible airway obstruction, but a certain number of asthmatics have evidence of residual airway obstruction²⁾. Especially, a continuous airway obstruction can be observed in chronic bronchial asthma patients³⁾. Bronchial asthma is known to be caused by chronic airway inflammation with eosinophilic infiltration⁴⁾. Chronic inflammation causes a remarkable airway remodeling⁵⁾ and it is closely related to the severity of the disease.

It is generally accepted that cigarette smoking⁷⁾ or airway inflammation⁸⁾ causes developing emphysema in asthmatics, However, asthmatics often show the characterristics of emphysema⁹⁾ and some emphysema patients show asthmatic characteristics such as wheezing or airway hyper-responsiveness so that it is controversial whether asthma progresses to emphysema¹⁰, ¹¹⁾. Chest plain X-ray of asthmatics showed normal or nonspecific findings, like pulmonary hyperinflation, which were not helpful in the diagnosis and evaluation of the progression in asthmatics¹²⁾. However, as the image diagnosis has been developed, the radiographic study of asthmatics is being actively performed, especially by using high-resolution computed tomography (HRCT). The recent study reported that airway inflation and emphysema are observed in HRCT finding and cigarette smoking can cause emphysema in asthmatics⁸⁾. A computed tomographicpathologic correlation in emphysema was also reported¹³⁾. So HRCT is known as a useful method in the quantitative and qualitative evaluation¹⁴⁾ of emphysema. It is difficult to discriminate between bronchial asthma and emphysema because their clinical features are similar and there is a possibility of a combination between the two diseases¹⁵⁾, of which clinical characteristics are not exactly known yet.

The purpose of this study is to evaluate the, clinical characteristics of asthmatics with emphysema and to identify any factors which affect the disease, except smoking. We evaluate the presence of emphysema or not in asthmatics by HRCT and compare the two groups with pulmonary function test and various clinical features.

Bronchial asthma presents chronic airway inflammation which is observed in all patients with asthma⁴⁾. This inflammation is already developed even in a mild form of asthma and increased according to the severity of the disease. Some damaged tissue, completely repaired in the beginning of the inflammatory response or others, is replaced with connective tissue to form a permanent scar¹⁹⁾. Remodeling of airway-like thickening of the smooth muscle with inflammation in the submucous tissue of the 8 airway and mucous gland hypertrophy and reorganization of extracellular matrix are reported⁵⁾ in patients with asthma. The occurrence of emphysema is closely related to the severity of the asthma and younger asthmatics have healing potential so that they have fewer scars according to the severity of the asthma than older people, which indicates that emphysema is partly related to age²⁰⁾. But, In this study, a significant difference was not observed between the two groups with and without emphysema according to age, duration of morbidity and severity.

It is reported that cigarette smoking is a main risk factor of chronic obstructive lung disease so 26% of heavy smokers developed to chronic obstructive pulmonary disease²¹⁾. However, its mechanism is not clearly explained yet and smoking is known to cause as imbalance of proteolytic-antiproteolytic activity and lead to pulmonary destruction and airway obstruction²²⁾. Auerbach et al.⁷⁾ reported that emphysema was not observed in 90% of nonsmokers and moderate emphysema was 2.9% of nonsmokers, whereas, in smokers, emphysema was not observed in only 0.3%, moderate emphysema in 32.7% and severe emphysema in 19.2% on autopsy findings, which revealed that smoking consumption and older age were related to the increase of the severity of emphysema. Mochizuki et al.¹⁰⁾ observed that among asthmatics, emphysema developed only in the heavy smokers. Lynch et al.²³⁾ presented that more significant emphysema was found in smokers with asthma than nonsmokers with asthma, but there were 2 cases of nonsmoker asthmatics which developed emphysema. Our study observed emphysema on HRCT in 6 patients (30%) out of 20 smokers with asthma and closely related with smoking (p=0.004) in case of asthmatics with emphysema. But a finding of emphysema was also observed in one nonsmoker with asthma.

In addition to smoking, there are some factors to cause chronic obstructive pulmonary disease, like old age, male, history of respiratory disease at infancy, occupational inhalation of specific dust, decrease of initial pulmonary function, air pollution and α1-protease deficiency²¹⁾. Some agents like talc and methylphenidate (Ritalin) are known, but the reason why some smokers have lower pulmonary function is not explained yet. It is accepted that there is a difference of susceptibility related to the unknown genetic factor²⁴⁾.

In this study, a nonsmoking asthmatic with emphysema on HRCT is a 35-year-old woman with 36 months of disease duration. She may have a possibility of passive smoke, but there is no clinically important²¹⁾ or other factor, except smoking, related to the development of emphysema²⁵⁾. There is a possibility of asthma induced emphysema or α₁-antitrypsin deficiency²², ²⁶⁾. However, we did not measure serum α₁-antitrypsin so we could not confirm the exact genesis. Cigarette smoking increases IgE and risk of asthma attack in workers who are exposed to specific work allergic antigens, like platinum or moisturizer-related antigens²¹⁾. It was reported that IgE concentration observed in patients with emphysema is related to the high frequency of smoking²⁷⁾. In this study, serum IgE is not significantly increased in asthmatics with emphysema compared to ones without emphysema, but it increased (p=0.076) so that it is thought to be related to the previous report²¹⁾ about the role of smoking to increase IgE and the risk of asthmatic attack. Generally, pulmonary function test for the airway obstruction in emphysema does not well reflect the anatomical abnormalities. Although 30% of lung parenchyme changed emphysema, symptoms of airway obstruction may not appear²⁸⁾, which is usually observed with centrilobular emphysema involving the upper lobe²⁹⁾ of the lung. Even in subjects with normal pulmonary function test, we can see the emphysema on HRCT³⁰⁾.

Diffusing capacity (DLco) is useful to diagnose emphysema and it is reported that visual inspection of emphysema in asthmatics is correlated to DLco/V_A in reverse⁸⁾ relation. It is known that mild emphysema can be detected by using HRCT and DLco³¹⁾. Mochizuchi et al.¹⁰⁾ presented that FEV₁, FEV₁/FVC, DLco/V_A were decreased significantly in asthmatics with severe emphysema and FEV₁/FVC decreased in a mild emphysema group. But our study did not show significant differences of FEV₁/FVC, TLC, DLco between two groups with and without emphysema diagnosed by HRCT. Normal lung function without a significant decrease of DLco may be due to an early period of emphysema³¹⁾, so it is difficult to evaluate the emphysematous change in asthmatics with pulmonary function test only.

In asthmatics, structural changes of the airway can be estimated by decreases in pulmonary function test and irreversible airflow obstruction, but they mostly show normal findings on chest plain films. It is reported that mild and moderate emphysema could be detected only in 16% based on chest plain X-rays and the severe emphysema could be diagnosed in 41%¹²⁾. As a result of comparison between chest computed tomography findings and pathologic findings of lung specimens after operations over the last 10 years, chest CT is the most accurate imaging method in diagnosing emphysema³²⁾. Recently, HRCT can be an index to evaluate the bronchial wall thickness and airway obstruction with more anatomical and physiological studies on asthmatics by indirect and non-invasive methods³³⁾. High-resolution computed tomography is known to be a good method to confirm physiologically significant emphysema²³, ³⁶⁾ and a good correlation between the view of HRCT in centrilobular emphysema with remodeling formation and pathologic finding has been reported³²⁾. In asthmatics, high-resolution computed tomography shows more abnormal findings related to permanent airway remodelings, like bronchodilation or bronchiectasis, compared to the normal group. Paganin et al.³⁴⁾ observed on HRCT that there were some reversible findings, like mucous impaction, ground-grass opacity, lobular atelectasis, that were not consistent with the degree of disease, whereas there were some irreversible findings like bronchiectasis, bronchial wall thickening, scarred opacity and emphysema that would be serious in severe bronchial asthma and non-allergic bronchial asthma. But the reports about irreversible findings on the bronchial wall thickening reveal different result.³⁵⁾ In our study, air trapping, bronchial wall thickening, fibrosis and ground-glass opacity were observed on HRCT in asthmatics. Lynch et al.²³⁾ reported that the incidence of emphysema in asthmatics is 19% on HRCT and our study showed a similar finding with 7 (12.1%) out of 58 patients.

Lynch et al.²³⁾ observed bronchial wall thickening in asthmatics by plain chest radiography (71%) and-by HRCT (92%) and presented that bronchial wall was more thickened in asthmatics. Choi et al.¹⁸⁾ reported that bronchial wall thickening appears with increased airway hyper-responsiveness at the time of the symptoms and there is no relation between duration of morbidity or age and bronchial wall thickness. They suggested that there is no significant difference in the bronchial wall thickness between asthmatics with and without emphysema. Our study showed a significantly increased finding (p=0.018) of bronchial wall thickening in bronchial asthma patients with emphysema, which is contrary to the result of Choi et al.¹⁸⁾ because it is assumed that subjects for our study had more severe asthma than those for the study of Choi et al¹⁸⁾.

Paganin et al.³⁴⁾ observed emphysema in nonsmokers with severe bronchial asthma and presented fibrosis in peribronchus and interstitial emphysema findings, which are related to scarred emphysema or airway remodeling. With regard to higher fibrosis appearance in bronchial asthma patients with emphysema, it is assumed that it is related to the fibrosis by tuberculosis in the past³⁷⁾.

Our study has concluded that emphysema in asthmatics is not related to the severity of bronchial asthma or duration of the disease, whereas it is closely related with cigarette smoking, but emphysema can occurr also by asthma itself, except smoking. Therefore, it has been determined that there is no difference of pulmonary diffusing capacity or pulmonary physiological index between the two groups with and without emphysema. But there are some limitations for our study. First, emphysema was not classified according to the severity of the disease so that we could not identify the relation between smoking and the severity of emphysema and the factors to discriminate between patients with mild emphysema and without emphysema. Second, HRCT finding is highly recognized in several studies, but any subjective interpretation can not be completely excluded. Third, serum α₁-antitrypsin deficiency was not measured so that the exact development of emphysema by α₁-antitrypsin deficiency could not be confirmed. In case of asthmatics with emphysema, FEV₁ decreases quickly compared to simple asthmatics and the prognosis is known to be bad due to the lower life expectancy³⁸, ³⁹⁾. As the change of emphysema can be developed by asthma itself except cigarette smoking, more studies should be needed for its genesis.