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High-Resolution CT Quantification of Bronchiectasis: Clinical and Functional Correlation¹

¹ From the Departments of Diagnostic Radiology (G.C.O., P.L.K.) and Medicine (M.C.Y., J.C.M.H., W.K.L., K.W.T.T.), University of Hong Kong, Queen Mary Hospital, 806, Administration Block, Hong Kong SAR, China; and Faculty of Medicine, University of Hong Kong (P.K.S.C., J.C.K.L.). Received September 24, 2001; revision requested November 26; final revision received March 27, 2002; accepted April 29. Supported by a Committee for Research and Conference grant from the University of Hong Kong. Address correspondence to K.W.T.T. (e-mail: kwttsang@hku.hk).

	ABSTRACT

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
PURPOSE: To evaluate clinical relevance of high-resolution computed tomographic (CT) findings in patients with bronchiectasis by using a quantitative high-resolution CT protocol to assess extent of bronchiectasis, severity of bronchial wall thickening, and presence of small-airway abnormalities and mosaic pattern.

MATERIALS AND METHODS: Sixty Chinese patients with steady-state bronchiectasis underwent thoracic high-resolution CT and lung function tests. Exacerbation frequency per year and 24-hour sputum volume were determined. Extent of bronchiectasis, severity of bronchial wall thickening, and presence of small-airway abnormalities and mosaic attenuation were evaluated in each lobe, including the lingula. Differences between sex and smoking status with respect to high-resolution CT, lung function, and clinical parameters were tested with either the independent sample t test or the Mann-Whitney test. Spearman rank correlation was used to evaluate associations between clinical, lung function, and high-resolution CT scores. Multiple regression analyses were performed to determine which high-resolution CT parameters would best predict lung function and clinical parameters, adjusted for smoking.

RESULTS: Exacerbation frequency was associated with bronchial wall thickening (r = 0.32, P = .03); 24-hour sputum volume with bronchial wall thickening and small-airway abnormalities (r = 0.30 and 0.39, respectively; P < .05); and forced expiratory volume in 1 second (FEV₁), ratio of FEV₁ to forced vital capacity (FVC), and midexpiratory phase of forced expiratory flow (FEF_25%-75%) (r = -0.33, -0.29, and -0.32, respectively; P < .05). Extent of bronchiectasis, bronchial wall thickening, and mosaic attenuation, respectively, were related to FEV₁ (r = -0.43 to -0.60, P < .001), FEF_25%-75% (r = -0.38 to -0.57, P < .001), FVC (r = -0.36 to -0.46, P < .01), and FEV₁/FVC ratio (r = -0.31 to -0.49, P < .01). After multiple regression analysis, bronchial wall thickening remained a significant determinant of airflow obstruction, whereas small-airway abnormalities remained associated with 24-hour sputum volume. Women had milder disease than men but showed more high-resolution CT functional correlations.

CONCLUSION: Findings of this study establish a link between morphologic high-resolution CT parameters and clinical activity and emphasize the role of bronchial wall thickening in patients with bronchiectasis.

© RSNA, 2002

Index terms: Bronchiectasis, 60.26 • Lung, CT, 60.12118

	INTRODUCTION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
The pathologic and functional hallmarks of bronchiectasis are irreversible abnormal bronchial dilatation and airflow obstruction, although mixed obstructive-restrictive or restrictive patterns of lung function can be found in a minority of patients (1–4). The exact pathophysiologic mechanism for the obstructive defect remains uncertain but is generally regarded as multifactorial (5,6). These factors include collapse of large airways at expiration (7), mucus retention (8), sputum proteases (9), bronchial mucosal thickening (6), airway hyperactivity or concurrent asthma (10,11), obliterative bronchiolitis (12,13), and emphysema (14,15).

High-resolution computed tomography (CT) has superseded bronchography as the method of choice for the morphologic evaluation of patients with both bronchiectasis and small-airway disease (13,16–21), with increasing interest shown in morphologic-functional evaluation in patients with not only these diseases but also asthma (5,6,12,22–26). The role of bronchial wall thickening as a determinant of airflow obstruction in patients with both asthma and bronchiectasis has been alluded to in some studies (6,24). In patients with bronchiectasis, sputum production is one clinical indicator of disease activity that has been shown to correlate with sputum inflammatory markers and circulating adhesion molecules (27,28). We hypothesize that airway remodeling in patients with bronchiectasis, as in those with asthma, forms the basis for the morphologic and functional abnormalities, with bronchial wall thickening as one manifestation of this process. The purpose of this study, therefore, was to evaluate the clinical relevance of high-resolution CT findings in patients with bronchiectasis by using a quantitative high-resolution CT protocol to assess extent of bronchiectasis, severity of bronchial wall thickening, and presence of small-airway abnormalities and mosaic pattern.

	MATERIALS AND METHODS

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Patients
Sixty consecutive Chinese patients (23 men, 37 women; mean age, 58 years ± 14 [SD]) who attended the Special Respiratory Clinic at Queen Mary Hospital, Hong Kong, China, and who received a clinical diagnosis of bronchiectasis were recruited with informed consent between January and December 1999. Of the 23 men (mean age, 59.4 years ± 13) and 37 women (mean age, 56.9 years ± 14.1), 47 never smoked and 13 were ex-smokers. This study was performed with institutional ethics committee approval. Each patient was examined during a baseline period (three consecutive weekly visits) to ensure that bronchiectasis was stable. During these visits, the patients were questioned about respiratory symptoms, including cough, dyspnea, hemoptysis, sputum production, chest pain, and wheezing.

In each patient, exacerbation frequency was the number of exacerbations that occurred in the preceding 12 months and was determined by means of history taking and review of clinical charts. An exacerbation was defined as a patient’s subjective assessment of persistent (24 hours) deterioration in at least three respiratory symptoms, including cough, dyspnea, hemoptysis, increased sputum purulence or volume, and chest pain. This definition was applied whether or not patients had fever (temperature, 37.5°C), radiographic findings suggestive of deterioration of the disease, systemic disturbances, or deterioration in physical signs in the chest, including the presence of crackles and dullness at auscultation and percussion (28,29). Age at onset and duration of disease were also determined.

Laboratory measurements included 24-hour sputum volume and lung function assessment. In all patients, inclusion criteria were confirmation of bronchiectasis on the basis of findings on a high-resolution CT scan, absence of asthma and other unstable systemic diseases, and presence of stable bronchiectasis (28). The latter was defined as a less than 10% alteration in 24-hour sputum volume, forced expiratory volume in 1 second (FEV₁), and forced vital capacity (FVC) and an absence of deterioration in respiratory symptoms at baseline visits (28). Exclusion criteria included age younger than 18 years, pregnancy, history of previous lung resections, and presence of other concomitant lung diseases, such as bronchial carcinoma, interstitial lung disease, active tuberculosis, lung destruction (affecting one lobe or more), or lobar consolidation at high-resolution CT. At high-resolution CT, the characteristics of bronchiectasis included the following findings: an internal bronchial diameter larger than the diameter of the accompanying pulmonary artery, a lack of tapering of bronchi, and the presence of bronchi in the outer third of the lung parenchyma (30–32).

High-Resolution CT
In the study, all patients underwent high-resolution CT of the thorax with a scanner (Hi-Speed Advantage; GE Medical Systems, Milwaukee, Wis), and they were in the supine position. Scanning parameters included collimation of 1 mm, section interval of 10 mm, 120 kV, and 220 mA. Expiratory scans were obtained in all patients by using similar parameters, except with a larger section interval (ie, 20 mm). Images were reconstructed into a bone algorithm, and films were obtained by using standard lung window settings (window level, -700 HU; window width, 1,000–1,500 HU).

High-Resolution CT Evaluation
Each lobe (ie, the lingula segment was considered as a separate lobe) of the lungs was separately evaluated for the extent of bronchiectasis and bronchial wall thickening. The presence of small-airway abnormalities and mosaic attenuation was also noted. Small-airway abnormalities included centrilobular opacities, tree-in-bud opacities, and bronchiolectasis (12,13,33–35), and mosaic attenuation was defined as the presence of alternating areas of hypoattenuation and hyperattenuation of the lung parenchyma. A radiologist with a special interest in thoracic radiology (G.C.O.) read all high-resolution CT images. The images were read in random order again 6 weeks after initial reading by the same reader, who was blinded to the initial evaluation scores to test for intraobserver variation. To evaluate interobserver error, a second experienced radiologist (P.L.K.), who was blinded to the scores of the first reader, independently reviewed high-resolution CT images of 20 randomly selected patients. Any differences in scores in these 20 patients were resolved by consensus.

The extent of bronchiectasis was quantified by first assigning a score to each of the six lobes according to the percentage (ie, grade) of lobar involvement, which was derived with the following scale: grade 0, none; grade 1, mild (<25%); grade 2, moderate (25%–50%); and grade 3, severe (>50% involvement of each lobe) (Fig 1). All individual lobar scores were summed to calculate the overall score for the extent of bronchiectasis. The thickness of the bronchial wall relative to the external diameter of dilated bronchi (EDB) perpendicular to the transverse plane was evaluated in each lobe. This score was determined with the following scale: grade 0, normal thickness; grade 1, thickness greater than 20% and less than 50% EDB; grade 2, thickness greater than 50% EDB; and grade 3, complete obliteration of the bronchial lumen (Fig 1). If there was a range of bronchial wall thickening noted in each lobe assessed, a mean score was calculated per lobe whereby the number of scores assigned was the denominator for the sum of all scores calculated. The sum of individual lobar bronchial wall thickening scores was the overall score for each patient (Fig 2).

View larger version (76K): [in this window] [in a new window] [Download PPT slide]   Figure 1. Schematic diagram depicts four grades of bronchial wall thickening scores.

View larger version (117K): [in this window] [in a new window] [Download PPT slide]   Figure 2a. Transverse high-resolution CT scans obtained in a 40-year-old man with bronchiectasis. (a) Scan shows small-airway disease denoted by centrilobular and tree-in-bud (black arrows) opacities and bronchiolectasis in the left upper lobe. Bronchiectasis in the upper lobe was assigned a grade of 1, with grade 1 (white arrows) bronchial wall thickening. In the apical segments of the lower lobes, grade 2 (arrowheads) bronchial wall thickening also is present. (b) Scan shows a combination of grade 1 (arrows) and 2 (arrowheads) bronchial wall thickening in the basal segments of the lower lobes with an overall bronchial wall thickening score of 1.5. The extent of bronchiectasis was evaluated as grade 3 in the right lower lobe and grade 2 in the left lower lobe. (c) Scan shows mosaic attenuation in both upper lobes. (d) Expiratory scan shows air trapping. The hypoattenuating areas (*) were confirmed to be caused by air trapping in d.

View larger version (114K): [in this window] [in a new window] [Download PPT slide]   Figure 2b. Transverse high-resolution CT scans obtained in a 40-year-old man with bronchiectasis. (a) Scan shows small-airway disease denoted by centrilobular and tree-in-bud (black arrows) opacities and bronchiolectasis in the left upper lobe. Bronchiectasis in the upper lobe was assigned a grade of 1, with grade 1 (white arrows) bronchial wall thickening. In the apical segments of the lower lobes, grade 2 (arrowheads) bronchial wall thickening also is present. (b) Scan shows a combination of grade 1 (arrows) and 2 (arrowheads) bronchial wall thickening in the basal segments of the lower lobes with an overall bronchial wall thickening score of 1.5. The extent of bronchiectasis was evaluated as grade 3 in the right lower lobe and grade 2 in the left lower lobe. (c) Scan shows mosaic attenuation in both upper lobes. (d) Expiratory scan shows air trapping. The hypoattenuating areas (*) were confirmed to be caused by air trapping in d.

View larger version (109K): [in this window] [in a new window] [Download PPT slide]   Figure 2c. Transverse high-resolution CT scans obtained in a 40-year-old man with bronchiectasis. (a) Scan shows small-airway disease denoted by centrilobular and tree-in-bud (black arrows) opacities and bronchiolectasis in the left upper lobe. Bronchiectasis in the upper lobe was assigned a grade of 1, with grade 1 (white arrows) bronchial wall thickening. In the apical segments of the lower lobes, grade 2 (arrowheads) bronchial wall thickening also is present. (b) Scan shows a combination of grade 1 (arrows) and 2 (arrowheads) bronchial wall thickening in the basal segments of the lower lobes with an overall bronchial wall thickening score of 1.5. The extent of bronchiectasis was evaluated as grade 3 in the right lower lobe and grade 2 in the left lower lobe. (c) Scan shows mosaic attenuation in both upper lobes. (d) Expiratory scan shows air trapping. The hypoattenuating areas (*) were confirmed to be caused by air trapping in d.

View larger version (100K): [in this window] [in a new window] [Download PPT slide]   Figure 2d. Transverse high-resolution CT scans obtained in a 40-year-old man with bronchiectasis. (a) Scan shows small-airway disease denoted by centrilobular and tree-in-bud (black arrows) opacities and bronchiolectasis in the left upper lobe. Bronchiectasis in the upper lobe was assigned a grade of 1, with grade 1 (white arrows) bronchial wall thickening. In the apical segments of the lower lobes, grade 2 (arrowheads) bronchial wall thickening also is present. (b) Scan shows a combination of grade 1 (arrows) and 2 (arrowheads) bronchial wall thickening in the basal segments of the lower lobes with an overall bronchial wall thickening score of 1.5. The extent of bronchiectasis was evaluated as grade 3 in the right lower lobe and grade 2 in the left lower lobe. (c) Scan shows mosaic attenuation in both upper lobes. (d) Expiratory scan shows air trapping. The hypoattenuating areas (*) were confirmed to be caused by air trapping in d.

View larger version (74K): [in this window] [in a new window] [Download PPT slide]   Figure 3a. Transverse high-resolution CT scans obtained in a 64-year-old man with established bronchiectasis. (a) Inspiratory high-resolution CT scan shows mosaic attenuation (*) in the left upper lobe, which is accentuated on the (b) expiratory scan. Extent of bronchiectasis was evaluated as grade 3 in the left upper lobe.

View larger version (73K): [in this window] [in a new window] [Download PPT slide]   Figure 3b. Transverse high-resolution CT scans obtained in a 64-year-old man with established bronchiectasis. (a) Inspiratory high-resolution CT scan shows mosaic attenuation (*) in the left upper lobe, which is accentuated on the (b) expiratory scan. Extent of bronchiectasis was evaluated as grade 3 in the left upper lobe.

Lung Function Tests
All study patients underwent lung function tests within a mean of 11.4 days ± 8.2 (range, 2–31 days) either before or after high-resolution CT evaluation. Lung function indices were measured between 10:00 and 11:00 AM by using the standard protocol recommended by the American Thoracic Society (36), with a SensorMedics 2200 package (SensorMedics, Yorba Linda, Calif). The spirometric and lung volume parameters were expressed as a percentage predicted that was based on the prediction equations of Da Costa (37).

Statistical Analysis
All high-resolution CT parameters were not normally distributed, whereas other parameters were normally distributed. The effect of differences between sex and smoking status on high-resolution CT parameters, lung function parameters, and other clinical parameters were tested by using either the independent sample t test or the Mann-Whitney test. Univariate analyses of the associations between clinical parameters (24-hour sputum volume and exacerbation frequency) with lung function tests and high-resolution CT scores were determined by using the Spearman rank correlation.

Multiple regression analyses were performed to determine which high-resolution CT parameters (FEV₁, FVC, FEV/FVC ratio, midexpiratory phase of the forced expiratory flow [FEF_25%-75%], and total lung capacity [TLC]) would best predict lung function and clinical parameters (24-hour sputum volume and frequency of exacerbations), adjusted for smoking. The five high-resolution CT parameters were correlated. However, the extent of bronchiectasis was highly correlated with each of the high-resolution CT parameters, and it was omitted as an independent variable. A P value less than .05 was considered to indicate a statistically significant difference. Intraclass reliability analysis was used to evaluate intraobserver variation, whereas interobserver reliability was evaluated by using the sign test.

	RESULTS

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Patient Characteristics
Complete data on exacerbation frequency were available in 52 patients. The mean exacerbation frequency for the whole group was 3.38 ± 3.24 in the preceding 12 months. The mean 24-hour sputum volume was 13.5 mL ± 20. All 60 patients underwent lung function tests. The means for the whole group were as follows: FEV₁, 74.3% ± 30; FVC, 84.6% ± 23.7; FEV₁/FVC ratio, 66.2% ± 16.2; FEF_25%-75%, 45.2% ± 31.7; residual volume (or RV), 119% ± 38; and TLC, 88.8% ± 17.6. In most patients, the data indicated an obstructive pattern of disease. Bronchiectasis was noted in all 60 patients and was in both lungs in 49 (82%) patients and in one lung in 11 (18%) patients. A total of 360 lobes were evaluated in 60 patients; of those, 214 (59%) lobes were bronchiectatic. The overall median scores for extent of disease (Fig 4), bronchial wall thickening (Fig 4), small-airway abnormalities (Fig 2), and mosaic attenuation (Fig 3) for the entire group were 7.0 (range, 0–18), 3.6 (range, 0–18), 1.6 (range, 0–6), and 2.0 (range, 0–6), respectively.

View larger version (94K): [in this window] [in a new window] [Download PPT slide]   Figure 4. Transverse high-resolution CT scan obtained in a 46-year-old man shows a combination of grades 1 (short arrow), 2 (long arrow), and 3 (arrowheads) bronchial wall thickening in the left lower lobe. Extent of bronchiectasis was evaluated as grade 1 in the right middle lobe and grade 2 in the left lower lobe. The right lower lobe was normal.

View larger version (15K): [in this window] [in a new window] [Download PPT slide]   Figure 5a. Scatterplots show the relationships between clinical and high-resolution CT parameters. (a) Scatterplot shows that increasing 24-hour sputum volume is associated with increasing small-airway abnormalities (r = 0.39, P = .004). (b) Scatterplot shows a similar relationship between exacerbation frequency and bronchial wall thickening (r = 0.29, P < .05).

View larger version (23K): [in this window] [in a new window] [Download PPT slide]   Figure 5b. Scatterplots show the relationships between clinical and high-resolution CT parameters. (a) Scatterplot shows that increasing 24-hour sputum volume is associated with increasing small-airway abnormalities (r = 0.39, P = .004). (b) Scatterplot shows a similar relationship between exacerbation frequency and bronchial wall thickening (r = 0.29, P < .05).

View larger version (22K): [in this window] [in a new window] [Download PPT slide]   Figure 6a. Scatterplots show the relationships between high-resolution CT and lung function parameters. An inverse relationship is shown between bronchial wall thickening and (a) FEV1 (r = -0.60, P <.001) and (b) FEF25%-75% (r = -0.57, P < .001), respectively. A similar relationship is shown between extent of bronchiectasis and (c) FEV1 (r = -0.55, P < .001)and (d) FEF25%-75% (r = -0.51, P < .001).

View larger version (22K): [in this window] [in a new window] [Download PPT slide]   Figure 6b. Scatterplots show the relationships between high-resolution CT and lung function parameters. An inverse relationship is shown between bronchial wall thickening and (a) FEV1 (r = -0.60, P <.001) and (b) FEF25%-75% (r = -0.57, P < .001), respectively. A similar relationship is shown between extent of bronchiectasis and (c) FEV1 (r = -0.55, P < .001)and (d) FEF25%-75% (r = -0.51, P < .001).

View larger version (22K): [in this window] [in a new window] [Download PPT slide]   Figure 6c. Scatterplots show the relationships between high-resolution CT and lung function parameters. An inverse relationship is shown between bronchial wall thickening and (a) FEV1 (r = -0.60, P <.001) and (b) FEF25%-75% (r = -0.57, P < .001), respectively. A similar relationship is shown between extent of bronchiectasis and (c) FEV1 (r = -0.55, P < .001)and (d) FEF25%-75% (r = -0.51, P < .001).

View larger version (22K): [in this window] [in a new window] [Download PPT slide]   Figure 6d. Scatterplots show the relationships between high-resolution CT and lung function parameters. An inverse relationship is shown between bronchial wall thickening and (a) FEV1 (r = -0.60, P <.001) and (b) FEF25%-75% (r = -0.57, P < .001), respectively. A similar relationship is shown between extent of bronchiectasis and (c) FEV1 (r = -0.55, P < .001)and (d) FEF25%-75% (r = -0.51, P < .001).

Multiple Regression Analysis
The results of multiple regression analyses are shown in Table 5. Bronchial wall thickening was the most significant determinant of FEV₁, FVC, FEV₁/FVC ratio, FEF_25%-75%, and TLC after adjustment for smoking. Mosaic attenuation was significantly associated with FEV₁ only, whereas high-resolution CT small-airway abnormalities were significantly associated with 24-hour sputum volume. High-resolution CT parameters were not related to the frequency of acute exacerbation. In men and women, relationships were different with respect to high-resolution CT, lung function test results, and clinical parameters. In women, bronchial wall thickening was significantly associated with FEV₁, FEV₁/FVC ratio, FEF_25%-75%, and TLC; mosaic attenuation, with FEV₁ and FVC; and high-resolution CT small-airway abnormalities, with 24-hour sputum volume. In men, bronchial wall thickening, but not other high-resolution CT parameters, was significantly associated with FEV₁, FEV₁/FVC ratio, FEF_25%-75%, and TLC.

	DISCUSSION

TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

Bronchiectasis is a poorly understood chronic but progressive inflammatory and infective airway disease that is common among Chinese. Findings in other studies (29,39,40) indicated that proinflammatory cytokines, which mediate airway infiltration through neutrophils, that include tumor necrosis factor and interleukins 1 and 8 are found in abundance in the sputum of patients with bronchiectasis. Findings of immunohistochemical studies of airways in patients with bronchiectasis also revealed increased airway infiltration and swelling through neutrophils, T lymphocytes, macrophages, and interleukin 8–positive cells (39,40). This cellular infiltration is harmful, as, for instance the release of neutrophil elastase in the airways correlates with disease activity and proinflammatory cytokine release in patients with steady-state bronchiectasis (28).

For the first time, to our knowledge, the respective relationships between 24-hour sputum volume and high-resolution CT parameters determined in this study indicate a link between high-resolution CT morphologic features and disease activity in patients with bronchiectasis. We postulate that inflammation in airway remodeling produces thickening of the medium and large bronchi, and in smaller airways, this thickening is expressed as centrilobular nodules and tree-in-bud opacities at high-resolution CT.

Current methods to assess cellular infiltration and disease activity in patients with airway disease generally require the use of bronchial biopsies and subsequent immunohistochemical studies. The findings in our study that bronchial wall thickening is the major determinant of airflow obstruction indicate that our high-resolution CT method of evaluating bronchial wall thickness could be used as a noninvasive technique for monitoring disease activity in patients with bronchiectasis.

In a study of 100 patients with bronchiectasis who were recruited in two countries, Roberts et al (6) used a similar but more complex visual assessment of inspiratory and expiratory high-resolution CT parameters. That assessment included extent of bronchiectasis, bronchial dilatation, bronchial thickening, mucus plugging and centrilobular plugging, airway collapse, and extent of mosaic attenuation. These investigators found that the severity of bronchial wall thickening and mosaic attenuation was independently correlated with airway obstruction; they concluded that small- and medium- rather than large-airway disease formed the basis of airflow obstruction in patients with bronchiectasis. However, clinical indicators of disease activity, such as 24-hour sputum volume, which may perhaps have a greater clinical importance in regard to the patient’s quality of life, were not evaluated.

At high-resolution CT, mosaic attenuation is the cardinal feature of bronchiolitis obliterans; in patients with bronchiectasis, mosaic attenuation has been suggested as the primary cause of airflow obstruction and air trapping (6,12). In this study, our findings suggest that mosaic attenuation is a predictor of lung function parameters of airflow obstruction in only women. In our study, high-resolution CT features of small-airway abnormalities of centrilobular nodules, tree-in-bud opacities, and bronchiolectasis were associated with only 24-hour sputum volume and not with airflow obstruction.

The lack of association between high-resolution CT small-airway abnormalities and lung function parameters could have been caused by present technical constraints on spatial resolution. As a result, thickening in the walls of terminal and respiratory bronchioles could not be appreciated at high-resolution CT, and, hence, these findings caused an underestimation of the presence of small-airway abnormalities. The findings of this study suggest that there may be two separate processes in patients with bronchiectasis: an ongoing airway inflammation and airway remodeling with bronchial wall thickening.

An interesting observation in this study is that there were sex differences with respect to small-airway abnormalities and lung function parameters in our patients with bronchiectasis. Among nonsmokers, women in this study had better lung function than did their male counterparts, which suggests they may have had a milder disease even though the duration of disease was not substantially different. Their lower scores in regard to all high-resolution CT parameters also supported this observation. Another difference was the finding that in women, but not in men, mosaic attenuation was associated with airflow obstruction and small-airway abnormalities were associated with 24-hour sputum volume.

Sex differences in patients with respect to airway behavior and clinical manifestations of airway diseases, although not widely reported, occur throughout the human life span (41). This is related to structural, functional, immunologic, and hormonal differences between the sexes. For example, as early as the neonatal period, girls and women have higher flow rates for a given lung volume than do boys and men (42,43), and this advantage persists throughout life. In women, the airway also is affected by hormonal factors from infancy through puberty to the postmenopausal period (41,44), with menstrual cycles, the oral contraceptive pill, and hormone replacement therapy exacerbating airway hyperresponsiveness and asthma (41). Susceptibility (ie, women were more susceptible) to the effects of smoking also may explain why female ex-smokers in our study had lower lung function compared with female nonsmokers. However, a similar difference was not evident in the men (45,46). Because there were only three female ex-smokers in the study, one cannot establish a conclusion related to the effects of smoking in patients with bronchiectasis.

In our study, smoking in the past may partly be responsible for the lung function abnormalities demonstrated in the 10 male ex-smokers; in these men, high-resolution CT changes of bronchiectasis were less severe than they were in nonsmokers, but the degree of airflow obstruction was not different. The longer duration of disease in male ex-smokers may be caused by the smoker’s chronic cough and phlegm being mistakenly reported as early onset of bronchiectasis.

In conclusion, morphometric high-resolution CT can be used for monitoring airflow obstruction and airway morphology in patients with bronchiectasis, and this modality can aid in the diagnosis of bronchiectasis. We believe that the results of this study provide a platform for further research into the relationship between the morphologic high-resolution CT features of bronchiectasis and airway biology, and findings from future studies might indicate that noninvasive monitoring of airway inflammation can be used in patients with bronchiectasis.

	ACKNOWLEDGMENTS

 
The authors thank the following people: the patients for their cooperation, the radiographers for their assistance in the CT imaging suite, Queen Mary Hospital staff members for invaluable assistance, Christina Fok, BHEc, for data collation, and Shelley Chan, MMedSci, for assistance in statistical analysis.

	FOOTNOTES

 
Abbreviations: EDB = external diameter of dilated bronchi, FEF_25%–75% = midexpiratory phase of forced expiratory flow, FEV₁ = forced expiratory volume in 1 second, FVC = forced vital capacity, TLC = total lung capacity

Author contributions: Guarantors of integrity of entire study, W.K.L., G.C.O., K.W.T.T.; study concepts, G.C.O., P.L.K., K.W.T.T., M.C.Y.; study design, G.C.O., P.L.K., K.W.T.T.; literature research, G.C.O., J.C.M.H., P.K.S.C., J.C.K.L.; clinical studies, G.C.O., K.W.T.T., P.L.K., J.C.M.H.; data acquisition, J.C.M.H., P.K.S.C., J.C.K.L.; data analysis/interpretation, G.C.O., P.L.K., P.K.S.C., J.C.K.L.; statistical analysis, G.C.O., M.C.Y.; manuscript preparation, G.C.O., P.L.K., J.C.M.H.; manuscript definition of intellectual content, M.C.Y., W.K.L.; manuscript editing, M.C.Y., W.K.L., K.W.T.T.; manuscript revision/review, M.C.Y., W.K.L.; manuscript final version approval, G.C.O., K.W.T.T., P.L.K., J.C.M.H., W.K.L.

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TOP ABSTRACT INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 

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