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High-Resolution CT Findings in Patients With Near-Fatal Asthma*: Comparison of Patients With Mild-to-Severe Asthma and Normal Control Subjects and Changes in Airway Abnormalities Following Steroid Treatment

Posted on: Friday, 7 January 2005, 03:00 CST

Study objectives: Extensive airway inflammation and excessive mucus production are implicated in deaths from asthma. High- resolution CT (HRCT) can be used to image both large and small airway abnormalities in asthmatics. The aims of this study were to clarify the distinction of HRCT features between near-fatal asthma (NFA) and non-NFA, and to evaluate serial follow-up HRCT scans of patients with NFA.

Patients and design: Abnormalities of the large airway (bronchial wall thickness) and small airways (prominence of centrilobular structures and air trapping) were measured semiquantitatively on HRCT scans of 24 non-NFA, 16 NFA, and 16 control subjects. In addition, these abnormalities were reevaluated after intensive and relatively long-term (> 6 months) treatment with inhaled corticosteroids.

Results: Prominence of centrilobular structures was observed in 36% of mild asthma cases, in 70% of moderate-to-severe asthma cases, and in 100% of NFA cases. Prominence of centrilobular structures, but neither bronchial wall thickness nor the area of air trapping, was significantly increased in NFA, as compared with mild or moderate-to-severe asthma (p < 0.05). In the seven non-NFA and five NFA patients who underwent follow-up HRCT scans, only bronchial wall thickness was decreased significantly in the NFA cases (p < 0.05), while bronchial wall thickness and the prominence of centrilobular structures were significantly decreased in the non-NFA cases. These small airway abnormalities were partially reversible in the both groups. Residual prominence of centrilobular structures after long- term inhaled corticosteroid treatment was significantly higher in NFA than non-NFA patients.

Conclusions: The results of our study indicate that extensive small airway abnormalities may be associated with NFA, and that these abnormalities are partially reversible after the successful control of asthma symptoms. (CHEST 2004; 126:1840-1848)

Key words: bronchial wall thickening; CT; near-fatal asthma; small airway

Abbreviations: BWI = bronchial wall index; HRCT = high- resolution CT; HU = Hounsfield unit; NFA = near-fatal asthma

Deaths from asthma continue to occur in spite of our increased understanding of the pathophysiology of asthma, the availability of more effective medications for the control of airway inflammation, and improved asthma education.12 To reduce asthma mortality rates, it is important to have a clear definition of the factors that predispose individuals to fatal asthma. A number of fatal asthma- related factors have been reported, which include previous history of life-threatening exacerbations, hospital admission within the previous year, inadequate management, and lack of access to medical care.3 However, there is currently no sensitive and specific assessment that reliably identifies patients who are prone to fatal complications. One of the reasons for this is that studies of asthma mortality are difficult due to the low death rates and incomplete information about the course of the disease in the period preceding death. Among the numerous factors that are potentially related to death, one of the most prominent features is a previous severe attack, as evidenced, for example, by a visit to an emergency department due to acute respiratory failure or hypoxic seizure.4,5 Thus, near-fatal asthma (NFA) appears to be a good model for the identification of pathologic and biological factors that represent predisposition to fatal asthma.

Patients who are dying of status asthmaticus have been reported as having increased smooth-muscle mass, extensive mucus plugging, and airway inflammation throughout the large and small airways.6,7 These changes are generally believed to reflect the severity of asthma, and they are most striking in patients who progress to fatal attacks.8,9 Since NFA is closely related to asthma-induced death, patients with NFA are presumed to have the same morphologic airway changes as patients with fatal asthma. However, since it is difficult to demonstrate these findings in NFA patients via the pathologic approach, the use of noninvasive tools is preferred. High- resolution CT (HRCT) scanning has proven to be the optimal noninvasive modality for the study of parenchymal and airway abnormalities in living patients with asthma. Changes in the large airways (bronchial wall thickening and bronchiectasis) and small airways (prominence of centrilobular structures, bronchioloectasis, and air trapping), and changes in the lung parenchyma (emphysema or ground-glass opacities), are detected frequently by HRCT in patients with mild-to-severe asthma.10 These HRCT findings accurately reflect the anatomic and physiologic changes in the airways and lung parenchymal tissues of patients with asthma.11 Regarding the airway wall thickening seen in HRCT scans, it has been reported that patients with a history of NFA have the same severity of wall thickening as those with moderate-to-severe persistent asthma.12 However, no comparative study has been conducted on small airway abnormalities such as prominence of centrilobular structures and air trapping, between NFA and non-NFA patients with the same degree of airflow limitation. In addition, no longitudinal study has been undertaken regarding the reversibility of these airway abnormalities by long-term treatments.

The aim of this study was to identity the HRCT findings that could be used to characterize NFA. The parameters of airway wall thickening, prominence of centrilobular structures, air trapping, bronchiectasis, emphysema, and ground-glass opacities were assessed either quantitatively or qualitatively on HRCT scans for NFA and non- NFA patients. In addition, changes in these abnormalities, its assessed on HRCT scans, were observed longitudinally over at least 6- month regimen of inhaled steroids.

MATERIALS AND METHODS

Subjects

We evaluated 40 patients with asthma and 10 normal healthy subjects. All of the asthmatic subjects met the definition of the American Thoracic Society.13 Each patient showed airway reversibility, as documented by an inhalant bronchodilator-induced improvement of FEV^sub 1^ > 15% and/or airway hyperreactivity of < 10 mg/mL (provocative concentration of methacholine causing a 20% fall in FEV^sub 1^). The severity of chronic persistent asthma was categorized as mild intermittent to severe persistent, based on the clinical features and the daily medication required for symptomatic control.14 This study included patients with mild asthma (group 1, n = 14), defined as those asthma patients who were classified into intermittent or mild persistent asthma, and patients with moderate- to-severe asthma (group 2, n = 10). defined as those asthma patients who were classified into moddate-or-severe persistent asthma, according to the guidelines for the diagnosis and management of asthma.14 NFA (group 3, n = 16) was defined as those asthma patients who were admitted to the ICU with acute respiratory failure, and who matched the following criteria: the presence of hypercapnia (PaCO^sub 2^ > 45 mm Hg, 5.9 kPa; normal range, 38 to 42 mm Hg), and signs of hypoxia (cyanosis or PaO^sub 2^ < 60 mm Hg, 7.9 kPa; normal range, 80 to 100 mm Hg),3,14 and duration of exacerbation of < 7 days. During the initial 7 days of treatment for NFA, steroids (2 mg/ kg/d of prednisolone or the equivalent dose of methylprednisolone) and aminophylline (5 mg/kg/d) were administered IV with concomitant inhalation of an aqueous β^sub 2^-agonist (salbutamol) on an as- needed basis. On the seventh day of treatment, the systemic steroid was replaced with an inhaled steroid. Patients with NFA underwent HRCT and pulmonary function testing after they had recovered from respiratory failure and had been weaned from the mechanical ventilator. Pulmonary function tests were performed on the same day as the HRCT scans, and at least 4 h after the last bronchodilator inhalation. Airway hyperresponsiveness was measured by the methacholine challenge test, which was carried out using the method of Chai and coworkers.15 The results were expressed as the provocative concentration of methacholine causing a 20% fall in FEV^sub 1^. which was measured 6 weeks after the presentation of NFA, except in cases where it had been measured previously. The healthy control subjects included hospital personnel (medical students and staff), who had normal spirometry and chest radiographic findings. Neither the normal control subjects nor the patients with chronic persistent asthma had any history of respiratory infection for at least 4 weeks before the study, and none of the participants smoked. This study was performed with the approval of the Ethics Committee of the University Hospital, and informed written consent was obtained from all enrolled subjects.

HRCT Scanning and Radiologic Evaluation

All of the subjects underwent HRCT scans of the chest (CT-W2000; Hitachi Medical; Tokyo, Japan) using the thin-section (1-mm collimation at 10-mm increments) technique, 120 kilovolt peak, 200 mA, 1-s scan time, 2.50- to 350-mm field of view, and a high- spatial-frequency algorithm. Expiratory CT scan was then performed at full exhalation from apices to the diaphragm with 20-mm increments. Ins\truction was given to the patient to fully exhale before each scan and to hold his/her breath at the end of exhalation. Explanations were given by the technician before the examination and training was performed to check whether full exhalation could be adequately obtained. The images were viewed at two window levels of -450 Hounsfield units (HU) for accurate measurement of bronchial diameters and -700 HU for analysis of other HRCT features. A window width of 1,350 to 1,700 HU was used.

The HRCT scans were evaluated for the presence and/or extent of the following features: (1) bronchial wall index (BWI) for bronchial wall thickening; (2) prominence of centrilobular structures for centrilobular branching linear structure and centrilobular nodule; (3) air trapping on expiratory scan; (4) bronchiectasis; (5) emphysema; and (6) ground-glass opacities (Fig 1). These findings were defined according to the glossary of terms recommended by the Fleischner society.16 Air trapping was defined as the abnormal retention of gas (< 100 HU compared to normal lung parenchyma) within a lung or lung units following exhalation. Bronchiectasis was diagnosed as the cylindrical, varicose, or cystic type. To diagnose bronchiectasis, the observers used not only the classical criterion based on the comparison of the diameters of the bronchial lumen and the homologous pulmonary artery, but also the absence of normal distal tapering of the bronchial lumen, as assessed on successive CT slices, and visualization of bronchi within 1 cm of the pleura. Emphysema was defined as a focal area of very low attenuation, usually without definable wall, that was surrounded by higher- attenuation normal lung parenchyma. Ground-glass opacity was defined as an area of hazy parenchymal opacity that did not obscure underlying vessels and airways.

FIGURE 1. A 29-year-old woman with bronchial asthma (group 1). Left, a: The full-inspiration HRCT scan shows diffuse bronchial wall thickening (arrows) and prominence of centrilobular structure (arrowheads, score 1) in the right lower lobe. Right, b: Expiratory HRCT scan shows geographic air trapping (arrows, score 2) at the same level of the right lower lobe.

The BWI (outer diameter - inner diameter/outer diameter) was used to compare bronchial wall thickening between the groups.17 The outer and inner luminal diameters were measured for all segmental and subsegmental bronchi with a luminal diameter of ≥ 1.5 mm. Only bronchi seen in cross-section were analyzed. We measured the bronchi that had maximum to minimum outer-diameter ratios of < 1.5, because the ratio of the longest to shortest diameter of the airway lumen is the usual way to predict roundness.18 The photographed CT images were magnified fivefold using an overhead projector, and measurements were made using a caliper. All measurements were done four times on one bronchus by two chest radiologists who had no knowledge of the group to which the subject belonged, and the mean values were recorded.

The lung was divided in six zones-upper, middle, and lower, right and left-by one third and two thirds of the vertical distance between the lung apices and the domes of the diaphragm for each patient. Each of these zones was evaluated and scored separately for the presence and/or extent of the HRCT features. Prominence of centrilobular structures and air trapping were scored according to the cross-sectional area of lung involved in each zone (0 = no involvement, 1 = 1 to 25%, 2 = 26 to 50%, 3 = 51 to 75%, and 4 = 76 to 100% of cross-sectional area).19,20 Score sheets were then tabulated. The total scores for centrilobular structures and air trapping ranged from 0 to 24, and the grade was derived by mean score of each lung zones. Grade 1 was defined for a total score of < 6. Grades 2, 3, and 4 were defined for total scores of 6 to 12, 13 to 18, and > 18, respectively. The air trapping in the superior segments of the lower lobes and isolated pulmonary lobules were not seored due to excluding of physiologic air trapping. The remaining HRCT features of emphysema, ground-glass opacities, and bronchiectasis were evaluated in terms of their presence or absence.

Two chest radiologists, who were blinded to the clinical features of the study subjects, interpreted the scans in an independent manner. The final score was obtained from the mean of the scores of the two observers.

Statistical Analysis

All of the statistical analyses were performed using a statistical software package (SPSS/PC WIN 8.0 package; SPSS; Chicago, IL). The results are represented as mean SE. Differences between the grades of abnormal CT findings and the clinical parameters were analyzed using analysis of variance. When significant differences were detected between the groups, the Mann- Whitney U test was performed. The Wilcoxon signed-rank test was used for paired samples. A Spearman rank correlation coefficient was calculated to evaluate the relationships between FEV^sub 1^ and BWI, prominence of centrilobular structures, and air trapping in patients with asthma. Differences were considered to be significant when the p value was < 0.05.

RESULTS

Relationship Between Airway Abnormalities on HRCT and Clinical Parameters and Pulmonary Function Tests

The characteristics of the study subjects are summarized in Table 1. The FEV^sub 1^ (percentage of predicted) values were lower in groups 2 and 3 than in group 1 (p < 0.05, respectively). The initial arterial blood gas analysis of the patients with NFA was 67.6 11.1 mm Hg (9.1 1.5 kPa) for PaCO^sub 2^ (range, 45.2 to 84.0 mm Hg; 6.1 to 11.2 kPa) and 47.9 8.4 mm Hg (6.4 1.2 kPa) for PaO^sub 2^ (range, 34.2 to 55.6 mm Hg; 4.6 to 7.4 kPa) in room air.

The interobserver agreements for the analysis of the HRCT findings were 76% for prominence of centrilobular structures, 71% for air trapping, 84% for bronchiectasis, 76% for emphysema, and 75% for ground-glass opacities. The κ values were > 0.75 for prominence of centrilobular structures, bronchiectasis, ground- glass density, and centrilobular emphysema, which represents excellent agreement. The κ values for air trapping were between 0.40 and 0.75, which represents fair-to-good agreement.21

Table 1-Demographic Characteristics of the Study Subjects*

No difference was found in the mean number of measured bronchi (20.5 6.3) among the study groups. The mean BWI values were 0.46 0.03 for group 1, 0.53 0.01 for group 2, and 0.55 0.02 for group 3, all of which were significantly higher (p < 0.05) than that of the control subjects (0.40 0.08) [Fig 2, left, A].

A prominence of centrilobular structures was observed in all patients with NFA (100%), but not in the normal control subjects. Prominence of centrilobular structures was observed in 36% of the patients in group 1, and 70% of the patients in group 2. The average grade of prominence of centrilobular structures was significantly higher in group 3 than in groups 1 and 2 (1.81 0.2 in group 3, 0.5 0.3 in group 1, and 1.0 0.3 in group 2, p < 0.05), and was similar in groups 1 and 2 (Fig 2, center, B). The frequency of air trapping was 78.6% (11 of 14 patients) in group 1, 80.6% (8 of 10 patients) in group 2, 81.3% (13 of 16 patients) in group 3, and 0% in the control group. Although the average grade of air trapping increased gradually according to the severity of asthma (1.78 0.4 in group 1, 1.8 0.3 in group 2, and 2.12 0.2 in group 3), there were no differences between the groups (Fig 2, right, C). Bronchiectasis was present in one case in group 3, and emphysema was present in only one case in group 2 and two cases in group 3. Ground-glass opacities were not found in any of the subjects.

The correlations between airway abnormalities on HRCT scans and the degree of airflow limitation FEV^sub 1^ (percentage of predicted) in groups 1, 2, and 3 were also evaluated. Of the parameters of BWI, prominence of centrilobular structures, and air trapping, only BWI was inversely correlated with FEV^sub 1^ (percentage of predicted) in groups 1 and 2 (r = - 0.78, p < 0.01). However, no correlation was found between BWI and FEV^sub 1^ (percentage of predicted) in group 3. Air trapping and prominence of centrilobular structures were not correlated with FEV^sub 1^ (percentage of predicted) in the asthma groups (Table 2).

FIGURE 2. Comparison of BWI (left. A), prominence of centrilobular strnetnre (center, B) and air trapping (right, C) between mild (group 1), moderate-to-severe (group 2), and patients with NFA (group 3). Control represents normal control subjects. NS indicates p > 0.05. *p < 0.05 vs group 1 or group 2. #p < 0.05 vs control.

Changes in Airway Abnormalities Following Long-term Inhaled Steroid Treatment

The HRCT scans were repeated for five patients from group 3, four patients from group 2, and three patients from group 1, after the clinical symptoms of asthma had remained under control for 6 to 12 months. Follow-up HRCT scans were obtained at the same levels as the initial CT scans, and the follow-up interval ranged from 7 to 24 months (mean, 16.8 months) after the initial HRCT scans. At the time of the follow-up HRCT scans, the patients from groups 1, 2, and 3 inhaled 257 85 g/d, 1,342 121 g/d, and 1,300 412 g/d, respectively, of hudesonide, or the equivalent dosages of fluticasone. All of the subjects were symptom free, and peak expiratory flow rate variability was < 20%.

Table 2-Correlation Coefficients Between the Airway Abnormalities on HRCT and FEV^sub 1^ Percentage of Predicted

The BWI (0.56 0.03 vs 0.48 0.01) and the level of prominence of centrilobular structures (1.14 0.3 vs 0.43 0.3) were decreased significantly after steroid treatment in groups 1 and 2 (p < 0.05, respectively; Fig 3, top left, A, and top center, B), although air trapping was not in these groups (2.0 0.4 vs 1.57 0.3, p > 0.05; Fig 3, top right, C). In group 3, only BWI (0.6 0.04 vs 0.54 0.\12) was decreased significantly (p < 0.05; Fig 3, bottom left, D), the levels of prominence of centrilobular structures (2.0 0.3 vs 1.4 0.4) and air trapping (2.2 0.2 vs 1.8 0.3) were unchanged (p > 0.05, respectively; Fig 3, bottom center, E, and bottom right, F). On follow-up, the BWI scores were still higher in groups 1 and 2 than in the control group (p < 0.05). All of the patients in group 3 had higher levels of prominence of centrilobular structures than grade 1 on the follow-up HRCT scans (Fig 3, bottom center, E), while three of seven patients from groups 1 and 2 had grade 1, and the remaining four subjects had grade 0 (Fig 3, top center, B). Despite steroid treatment, the initially elevated air trapping percentage was not normalized in all of the asthmatic subjects, regardless of the severity of the disease (Fig 3, top right, C, and bottom right, F).

FIGURE 3. Changes of BWI, prominence of centrilobular structure, and air trapping on HRCT over a mean interval of 16.8 months (range, 7 to 24 months) of treatment with inhaled steroid in patients with groups 1 and 2 (fop left. A; top center, B; and top right, C) and group 3 (bottom left, D; bottom center, E; and bottom right, F). NS indicates p > 0.05.

DISCUSSION

Our study demonstrates that the abnormalities seen on HRCT scans, such as bronchial wall thickening, air trapping, and prominence of centrilobular structures, are more extensive in all groups of asthma patients than in normal control subjects, regardless of the severity of the disease. One interesting finding is that NFA patients exhibited more severe prominence of centrilobular structures than did patients with moderate-to-severe asthma, with the same FEV^sub 1^ values, although there were no significant differences in the BWI and air-trapping parameters. The HRCT finding of prominence of centrilobular structures in asthmatic patients has not received much attention. Lynch et al22 reported that 10% of asthmatic patients had a prominence of centrilobular structures, whereas Grenier et al23 and Harmanci et al24 reported that at least 20% of asthmatic patients fell into this category. In the present study, 36% of patients with mild asthma and 70% of patients with moderate-to- severe asthma had a prominence of centrilobular structures. The incidence of prominence of centrilobular structures in our study is much higher than that reported previously.22-24 This may be due to different HRCT scanning methods and analyses. We analyzed quantitatively the HRCT scans for a 10-mm interval of entire lungs, which is a substantially larger overall lung area than those analyzed in the other studies. Prominence of centrilobular structures on HRCT may be due to intrabronchiolar mucoid impaction, peribronchiolar inflammation, and bronchiolar wall remodeling, which includes muscular hypertrophy. In support of this concept, pathologic studies of asthma patients who were dying of status asthmaticus showed severe air trapping and atelectasis, which are related to the plugging of small bronchi and bronchioles with tenacious inflammatory debris. In addition, the inflammatory debris consisted of plasma exudates and inflammatory cells, particularly eosinophils and epithelial cells that were sloughed from the airway surface.25,26 Mucosal biopsies demonstrated the presence of marked eosinophilic inflammation in the small airways of patients with mild asthma.27,28 In addition to airway inflammation, remodeling, and especially collagen deposition, smooth-muscle hypertrophy was also found throughout the peripheral airways.8,28,29 It is generally believed that the structural airway changes seen in postmortem or surgically resected lungs of patients with severe asthma have more profound physiologic consequences in the distal small airways than in the proximal large airways.30 These pathologic changes are most striking in cases that progress to fatal attacks.8 In the present study, all of the patients with NFA revealed prominence of centrilobular structures on HRCT scans. To our knowledge, the prominence of centrilobular structures on HRCJT scans has not been analyzed previously in patients with NFA. The results of this study suggest that extensive small airway changes may be associated with NFA, and that these changes are reflected by prominence of centrilobular structures on HRCT scans.

We also observed increases in air trapping and BWI in patients with moderate-to-severe asthma, and even in those with mild asthma, as compared to the normal control subjects. Air trapping can also be seen in normal subjects, although its extent is limited. Focal areas of relative lucency can be seen in normal subjects on expiratory scans in the superior segments of the lower Iobes.31 In a study by Lucidarme et al32- of 10 normal nonsmokers, excluding the superior segments of the lower lobes and isolated pulmonary lobules, no air trapping was visible. It is postulated that the slender segments may be less well ventilated than the adjacent lung, having a tendency to trap air during exhalation.

However, there were no significant differences in HWI between the patients with NFA and those with moderate-to-severe asthma, which corroborates the previous findings of Awadh and coworkers.12 BWI was measured mainly in the large airways, which encompassed the segmental and subsegmental bronchi. Large airway wall thickening is attributed to thickening of the basement membrane, goblet-cell hyperplasia, hypertrophy of the submucosal glands, and bronchial smooth-muscle hyperplasia.33 Dunnill and colleagues showed a quantitative difference in bronchial wall thickness between patients with status asthmaticus and patients with chronic bronchitis. Enlargement of the mucous gland was observed in both groups, but only in patients with status asthmaticus was there a marked increase in smooth-muscle volume, which accounts for 20% of the bronchial wall in certain cases.35 Airway wall thickening may he a major determinant of airway narrowing, airflow limitation, and symptom seventy in asthmatic patients.10,35,36 In our study, derangement of FEV^sub 1^ correlated strongly with BWI in patients with mild-to- severe persistent asthma, which is in good agreement with the results of previous studies.11,37 However, we could not find any significant difference in the BWI values between the groups of patients with asthma, which indicates that bronchial wall thickening is not a contributory factor to NFA, but is a basic underlying change in all asthma groups, including mild asthmatics. In our study, FEV^sub 1^ did not correlate with the grade of prominence of centrilobular structures or extent of air trapping in patients with NFA, which suggests that airilow limitation in NFA cases are probably not determined by a single abnormality, such as bronchial wall thickness, but instead appears to be determined by multifactorial abnormalities of the airways.7-9

Paganin et al10,35 considered bronchial wall thickening in asthmatic patients as an irreversible structural abnormality, although bronchial wall thickening has also been described as being reversible.38 The reversibility of bronchial wall thickening depends on the underlying pathologic features. It appears to be reversible when submucosal inflammation or edema predominate, and irreversible when the airways are remodeled extensively. Faganin and colleagues10,35 reported on the evolution of CT abnormalities after antiasthmatic' therapy. Un follow-up within 1 week or 2 weeks, mucoid impaction, acinar patterns, and lobar collapse were reversible, while bronchial wall thickness, bronchiectasis, and emphysema were unchanged. The reversibility of remodeled airways is supported in part by a pathologic study39 showing that subepithelial collagen deposition, which is one component of bronchial wall thickening, was reduced significantly in asthmatic patients who had undergone intensive anti-inflammatory therapy. However, no study has been undertaken on the changes in airway abnormalities over a relatively long period (6 months) following intensive anti- inflammatory therapy. Our results reveal that bronchial wall thickening is partially reversible in asthmatic patients, regardless of disease seventy. However, air trapping was not improved in the non-NFA and NFA patients, which suggests that air trapping is more refractive than bronchial wall thickening to steroid therapy. The different responses of the airway abnormalities to inhaled steroid therapy may be due to differences in the invoked sites, i,e bronchus vs bronchiole. The lack of impact of inhaled steroid treatment on air trapping may not be due to the duration of treatment, but rather appears to be due to a lack of penetration of the inhaled steroid into the peripheral airways.40,41 In the present study, the extent of prominence of centrilobular structures decreased during the treatment period, but did not attain the normal level (grade 0) in 43% of the non-NFA patients and in 100% of the patients with NFA. The extent of residual prominence of centrilobular structures was significantly more pronounced in the NFA patients than in the non- NFA patients, which indicates that remodeled small airways are more refractory to intensive and prolonged corticosteroid treatment in NFA patients than in non-NFA patients. The limiting factor of our study should be noted. Since only the bronchi seen in cross-section were analyzed, and only 10% of the lungs were imaged, many bronchi were not analyzed.

In conclusion, among the HRCT findings of airway abnormalities, only the severity of prominence of centrilobular structures differed significantly between the patient groups of NFA, mild, and moderate- to-severe asthma. The small airway abnormalities on HRCT scans may be partially reversible following intensive and relatively long- term treatment. However, these findings are not equally applicable to both NFA and non-NFA patients. NFA patients have lower responsesto steroid treatment than non-NFA patients. The exact nature of the small airway abnormalities remains to be elucidated in asthmatic patients, especially in patients with a previous history of NFA.

* From the Asthma and Allergy Research Group (Drs. Lee, S-W Park, Uh, Kim, and C-S Park), Department of Radiology (Drs. J-S Park and Hwang), Soonchunhyang University Hospital, Seoul and Bucheon, Korea.

REFERENCES

1 Sly RM, O'Donnell R. Stabilization of asthma mortality. Ann Allergy Asthma Immunol 1997; 78:347-354

2 McFadden ER Jr, Warren EL. Observations on asthma mortality. Ann Intern Med 1997; 127:142-147

3 Molfino NA. Near-fatal asthma. In: Hall JB, Corbridge TC, Rodrigo C, et al, eds. Acute asthma: assessment and management. New York, NY: McGraw-Hill, 2000; 29-47

4 Strunk RC, Mrazek DA, Fuhrmann GS, et al. Physiologic and psychological characteristics associated with deaths due to asthma in childhood: a case-controlled study. JAMA 1985; 254:1193-1198

5 Castro M, Schechtman KB, Halstead J, et al. Risk factors for asthma morbidity and mortality in a large metropolitan city. J Asthma 2001; 38:625-635

6 Dunnill MS. The pathology of asthma with special reference to changes in the bronchial mucosa. J Clin Pathol 1960; 13:27-33

7 James AL, Pare PD, Hogg JC. The mechanics of airway narrowing in asthma. Am Rev Respir Dis 1989; 139:242-246

8 Carroll N, Elliot J, Morton A, et al. The structure of large and small airways in nonfatal and fatal asthma. Am Rev Respir Dis 1993; 147:405-410

9 Carroll N, Carello S, Cooke C, et al. Airway structure and inflammatory cells in fatal attacks of asthma. Eur Respir J 1996; 9:709-715

10 Paganin F, Trussard V, Seneterre E, et al. Chest radiography and high resolution computed tomography of the lungs in asthma. Am Rev Respir Dis 1992; 146:1084-1087

11 Kasahara K, Shiba K, Ozawa T, et al. Correlation between the bronchial subepithelial layer and whole airway wall thickness in patients with asthma. Thorax 2002; 57:242-246

12 Awadh N, Mller NL, Park CS, et al. Airway wall thickness in patients with near fatal asthma and control group: assessment with high resolution computed tomographic scanning. Thorax 1998; 53:248- 253

13 American Thoracic Society. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease (COPD) and asthma. Am Rev Respir Dis 1987; 136:225-244

14 National Institutes of Health. Global strategy for asthma management and prevention, NHLBI/WHO workshop report, Bethesda, MD: National Heart, Lung, and Blood Institute, 2002; publication No. 02- 3659

15 Chai H, Farr RS, Froehlich LA, et al. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol 1975; 56:323-327

16 Austin JH, Mller NL, Friedman PJ, et al. Glossary of terms for CT of the lungs: recommendations of the Nomenclature Committee of the Fleischner Society. Radiology 1996; 200: 327-331

17 Boulet LP, Belanger M, Carrier G. Airway responsiveness and bronchial-wall thickness in asthma with or without fixed airflow obstruction. Am J Respir Crit Care Med 1995; 152:865-871

18 McNamara AE, Muller NL, Okazawa M, et al. Airway narrowing in excised canine lungs measured by high-resolution computed tomography. J Appl Physiol 1992; 73:307-316

19 Jensen SP, Lynch DA, Brown KK, et al. High-resolution CT features of severe asthma and bronchiolitis obliterans. Clin Radiol 2002; 57:1078-1085

20 Hansell DM, Wells AU, Rubens MB, et al. Bronchiectasis: functional significance of areas of decreased attenuation at expiratory CT. Radiology 1994; 193:369-374

21 Dawson-Saunders B, Trapp RG. Basic and clinical biostatistics. Norwalk, CT: Appleton & Lange, 1990; 58-59

22 Lynch DA, Newell JD, Tschomper BA, et al. Uncomplicated asthma in adults: comparison of CT appearance of the lungs in asthmatic and healthy subjects. Radiology 1993; 188:829-833

23 Grenier P, Mourey-Gerosa I, Benali K, et al. Abnormalities of the airways and lung parenchyma in asthmatics: CT observations in 50 patients and inter- and intraobserver variability. Eur Radiol 1996; 6:199-206

24 Harmanci E, Kebapci M, Metintas M, et al. High-resolution computed tomography findings are correlated with disease severity in asthma. Respiration 2002; 69:420-426

25 Hogg JC, Hegele RG. Postmortem pathology. In: Barnes PJ, Grunstein MM, Leff AR, et al, eds. Asthma. Philadelphia, PA: Lippincott-Raven. 1997; 201-220

26 Jeffery P. Morphology of the airway wall in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1991; 143:1152-1158

27 Hamid Q, Song Y, Kotsimbos TC, et al. Inflammation of small airways in asthma. J Allergy Clin Immunol 1997; 100:44-51

28 Kraft M. The distal airways: are they important in asthma? Eur Respir J 1999; 14:1403-1417

29 Kuwano K, Bosken CH, Pare PD. et al. Small airways dimensions in asthma and in chronic obstructive pulmonary disease. Am Rev Respir Dis 1993; 148:1220-1225

30 Wiggs BR, Bosken C, Pare PD, et al. A model of airway narrowing in asthma and chronic obstructive pulmonary disease. Am Rev Respir Dis 1992; 145:1251-1258

31 Webb WR, Muller NL, Naidich DP. High resolution computed tomography findings of lung disease. In: Webb WR, Muller NL, Naidich DP, eds. High resolution computed tomography of the lung. 3rd ed. Philadelphia, PA: Lippincott William & Wilkins, 2001; 175-177

32 Lucidarme O, Grenier PA, Cadi M, et al. Evaluation of air trapping at CT: comparison of continuous-versus suspended- expiration CT techniques. Radiology 2000; 216:768-772

33 Molet S, Hamid Q. Role of airway remodeling in severe asthma. In: Szefler SJ, Leung DYM, eds. Severe asthma: pathogenesis and clinical management. 2nd ed. New York, NY: Marcel Dekker, 2001; 89- 124

34 Dunnill MS, Massarella GR, Anderson JA. A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis and in emphysema. Thorax 1969; 24:176-179

35 Paganin F, Seneterre E, Chanez P, et al. Computed tomography of the lungs in asthma: influence of disease severity and etiology. Am J Respir Crit Care Med 1996; 153:110-114

36 James A, Carroll N. Theoretic effects of mucus gland discharge on airway resistance in asthma [abstract]. Chest 1995; 107(3 suppl):110S

37 Gono H, Fujimoto K, Kawakami S, et al. Evaluation of airway wall thickness and air trapping by HRCT in asymptomatic asthma. Eur Respir J 2003; 22:965-971

38 Bousquet J, Jeffery PK, Busse WW, et al. Asthma: from bronchoconstriction to airways inflammation and remodeling. Am J Respir Grit Care Med 2000; 161:1720-1745

39 Hoshino M, Takahashi M, Takai Y, et al. Inhaled corticosteroids decrease subepithelial collagen deposition by modulation of the balance between matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 expression in asthma. J Allergy Clin Immunol 1999; 104:356-363

40 Claman DM, Boushey HA, Liu J, et al. Analysis of induced sputum to examine the effects of prednisone on airway inflammation in asthmatic subjects. J Allergy Clin Immunol 1994; 94:861-869

41 Fahy JV, Boushey HA. Effect of low-dose beclomethasone dipropionate on asthma control and airway inflammation. Eur Respir J 1998; 11:1240-1247

Young-Mok Lee, MD, PhD; Jai-Soung Park, MD, PhD; Jung-Hwa Hwang, MD, PhD; Sung-Woo Park, MD; Soo-taek Uh, MD, PhD; Yong-Hoon Kim, MD, PhD; and Choon-Sik Park, MD, PhD

Drs. Lee and J-S Park contributed equally to this work.

This study was supported by a grant (01-PJ10-PG6-01GN14-000.3) from the Korean Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea.

Manuscript received March 5, 2004; revision accepted July 14, 2004.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (e-mail: permissions@chestnet.org).

Correspondence to: Choon-Sik Park, MD, Professor, Division of Allergy and Respiratory Medicine, Soonchunhyang University Hospital, 1174 Jung-Dong, Wonmi-Gu, Bucheon, Gyeonggi-Do 420-767, Republic of Korea; e-mail: schalr@schbc.ac.kr

Copyright American College of Chest Physicians Dec 2004

Source: Chest

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