Capecitabine as salvage treatment for lymphoepithelioma-like carcinoma of lung.

Lymphoepithelioma-like carcinoma (LELC) of lung has previously demonstrated good clinical response to 5-fluorouracil containing chemotherapy regimen, similar to the observation in undifferentiated nasopharyngeal carcinoma. Capecitabine, which is converted into active 5-fluorouracil within tumor cells, has been found effective in colorectal, breast, and recently nasopharyngeal carcinomas. We report our experience in five patients with advanced or metastatic LELC of lung who were treated with single agent capecitabine as salvage chemotherapy. The finding of disease control in three of five patients, especially with exceptionally durable stable disease (14.8 months) in one patient, suggests the potential clinical activity of capecitabine in LELC of lung. Future studies on capecitabine-containing chemotherapy regimens in LELC of lung are warranted.

Chinese green tea ameliorates lung injury in cigarette smoke-exposed rats.

BACKGROUND: Epigallocatechin-3-gallate (EGCG), which has been shown to have potent antioxidant effect, comprises 80% of catechins in Chinese green tea. This study was to investigate whether cigarette smoke (CS) exposure would induce lung morphological changes and oxidative stress in the CS-exposed rat model, and whether Chinese green tea (Lung Chen tea with EGCG as its main active ingredient) consumption would alter oxidative stress in sera and lung leading to protection of CS-induced lung damage. METHODS: Sprague-Dawley rats were randomly divided into four groups, i.e. sham air (SA), 4% CS, 2% Lung Chen tea plus SA or 4% CS. Exposure to SA or 4% CS was performed for 1h/day for 56 days in ventilated smoking chambers. Sera and lung tissues were collected 24h after last CS exposure for histology and all biochemical assays. RESULTS: Airspace enlargement and goblet cell hyperplasia were observed after 56-day CS exposure alone, which were abolished in the presence of green tea consumption. Serum 8-isoprostane level was significantly elevated (p<0.01) as well as lung superoxide dismutase (SOD) and catalase activities in CS-exposed rats compared to SA-exposed rats (p<0.05), which returned to the levels of SA-exposed rats after Chinese green tea consumption. CONCLUSION: These results indicate that increased levels of systemic oxidative stress after CS exposure play an important role in the induction of lung damage. Chinese green tea may have the ability to suppress CS-induced oxidative stress that leads to protection of lung injury.

Lung cancer: future directions.

Increasingly, basic research is being translated into clinical benefits for patients. Recent studies have shed more light on the clinical use of targeted therapies such as tyrosine kinase and angiogenesis inhibitors, and predictive factors for their clinical benefit and their role in different clinical settings are now being elucidated. New insights into the basic biology of lung cancer hold translational promise in risk assessment, early detection, molecular staging, treatment response prediction and novel therapies. New targeted agents directed at apoptotic and developmental pathways have the potential to exploit newly discovered vulnerabilities in the basic machinery of cancer. In addition, exploration of the cancer stem cell phenomenon in lung cancer may generate new approaches to prevent recurrence in surgically respectable lung cancer, and for the long-term control of extensive disease. Molecular profiling may also allow for highly individualized prognostic, predictive and therapeutic treatment plans tailored for each patient based on the molecular diagnostic profile of their tumour. Advances in genetic susceptibility, early detection and individualized therapy based on each tumour's unique biological properties all hold promise for the future management of lung cancer.

Lymphoepithelioma-like carcinoma of the lung.

Lymphoepithelioma-like carcinoma (LELC) of the lung was first reported in 1987. In the past two decades, there have been just more than 150 cases reported in the literature. This uncommon but distinct form of non-small cell lung carcinoma has a predilection for young non-smoking Asians, without gender distinction. Histologically, it is indistinguishable from undifferentiated nasopharyngeal carcinoma. The carcinogenic role of latent Epstein-Barr virus infection in causing LELC of the lung has been evident almost exclusively in Asians compared with Caucasians. Among the reported cases, more than half were in early resectable stages (I or II) and there was a tendency for peribronchovascular spread with vascular encasement in advanced diseases. In order to establish the diagnosis of LELC of the lung, both nasopharyngeal carcinoma and lymphoma have to be excluded by endoscopic biopsy (with or without magnetic resonance imaging of the nasopharynx) and immunohistochemical staining of the biopsy samples. The mainstay of treatment for early-stage disease is curative surgical resection, whereas multimodality treatment (surgery, chemotherapy, radiotherapy) has been adopted in advanced or metastatic diseases. The overall survival is more favourable in LELC of the lung compared with non-LELC type of non-small cell lung carcinoma. Future collaborative studies especially on optimizing treatment for this uncommon malignancy are clearly warranted.

Inhibition of pyocyanin-potentiated IL-8 release by steroids in bronchial epithelial cells.

Airway epithelial cells are the first targets of environmental stimuli and local cytokines. Pyocyanin-induced synergism with interleukin (IL)-1 or tumour necrosis factor (TNF) in triggering IL-8 release has been documented previously. In this study, IL-8 mRNA and protein expression were examined in cultured human bronchial epithelial cells (BEAS-2B) stimulated with pyocyanin alone, and in combination with IL-1beta or phorbol 12,13-dibutyrate (PDBu) in the absence and presence of a group of glucocorticoids. IL-8 mRNA was measured by RT-PCR, and IL-8 protein by ELISA (cell supernatants). Pyocyanin alone produced no increase in IL-8 mRNA and release. However, pyocyanin upregulated the stimulatory effect of IL-1beta or PDBu on the release of IL-8 in a dose-dependent manner. The stimulatory effect of pyocyanin on the IL-1beta- or PDBu-stimulated IL-8 release was reduced in the presence of dexamethasone, budesonide, and fluticasone. Budesonide and fluticasone were 10-fold more potent than dexamethasone. The protein kinase C (PKC) inhibitor, Go6976, also significantly reduced the stimulatory effect of pyocyanin on IL-1beta, and PDBu increased IL-8 release. In conclusion, this study shows that PKC signal pathway seems to be involved in the pyocyanin-mediated upregulation of the IL-1beta and PDBu-induced IL-8 release in BEAS-2B cells. These findings suggest that a vicious cycle perpetuating inflammation may exist in the biologic milieu of bronchiectatic patients infected with Pseudomonas aeruginosa due to the production of pyocyanin. The priming action of pyocyanin appears to be blocked by glucocorticoids, thus providing in vitro data in support of the clinical efficacy of inhaled glucocorticoids as anti-inflammatory drugs.

Analysis of TGF-beta(1) gene polymorphisms in Hong Kong Chinese patients with asthma.

BACKGROUND: The C-509T polymorphism of TGF-beta(1) gene has been associated with asthma and atopy in white populations. OBJECTIVE: We investigated the association between asthma and previously identified polymorphisms at C-509T and T869C of the TGF-beta(1) gene among 250 Chinese patients with asthma and 308 healthy controls in Hong Kong. METHODS: Genotyping was performed on peripheral blood genomic DNA by using PCR-RFLP. RESULTS: There were no differences in the frequencies of genotypes and alleles between patients and controls. The C-509T and T869C polymorphisms were in tight linkage disequilibrium (P < .01). Among atopic subjects, significant differences were found in genotype and allele frequencies for T869C polymorphism between patients and controls (P = .014 and P = .019, respectively), and individuals bearing the CC genotype were associated with increased risk for the development of asthma (odds ratio, 2.58; 95% CI, 1.17-5.66; P = .018) after adjusting for age, sex, and smoking status. Individuals with asthma bearing the CT genotype of the C-509T polymorphism had significantly increased risk for severe airflow obstruction compared with individuals who had mild obstruction (odds ratio, 4.00; 95% CI, 1.06-15.08; P = .035). CONCLUSION: Our results indicate that the polymorphisms at C-509T and T869C of the TGF-beta(1) gene are associated with asthma susceptibility in atopic subjects of the Hong Kong Chinese population, and the C-509T polymorphism may play a role in the pathogenesis of airflow obstruction.

Malignant mesothelioma in Hong Kong.

Malignant mesothelioma (mesothelioma) is rare. We conducted the first systematic study of the epidemiology of mesothelioma in Hong Kong from 1988 to May 2002 by reviewing medical records. Mesothelioma patients were identified from the database of 12 out of 20 hospitals that would have admitted mesothelioma patients territory-wide. These 12 hospitals served 73% of the total hospital bed-years of the 20 hospitals. We identified 67 mesothelioma patients. The estimated annual incidence was one per million, which was similar to the background incidence of one to two per million among Caucasians. Occupational history was available in 43 subjects. Three quarters of mesothelioma patients with available occupational history had occupational asbestos exposure. Restricting analysis to 48 patients with accessible medical records and using 67 occupational asbestosis patients for comparison, the epidemiology of mesothelioma in Hong Kong shares similarities with the literature: mean age of 63 years upon diagnosis, mean latency of 46 years, median survival of 9.5 months, male predominance, selective presentation among women, high prevalence among workers in ships and dockyards, predominantly epithelioid type, lower prevalence of asbestos bodies, and negative association with pleural plaques. Asbestos consumption in Hong Kong rose in the 1970s and peaked in early 1980s and late 1990s. Hong Kong may encounter an epidemic of mesothelioma in the 2010s if effective occupational asbestos control measures are not in place.

Elevated levels of transforming growth factor-beta(1) in serum of patients with stable bronchiectasis.

Bronchiectasis is a chronic inflammatory and infective airway disease characterized by irreversible dilatation of the bronchi and persistent purulent sputum. Transforming growth factor-beta(1) (TGF-beta(1)) has been found to be increased in the lungs or bronchoalveolar lavage fluid of patients with inflammatory lung diseases. However, little is known on the serum TGF-beta(1) levels in patients with bronchiectasis. We aimed to determine the serum TGF-beta(1) concentrations in 95 patients with stable bronchiectasis (63 women; mean+/-sd age, 58.9+/-14.1 years) and 68 control subjects (23 women; 48.9+/-12.8 years) by ELISA, and to correlate with clinical parameters. The serum TGF-beta(1) levels were significantly higher in bronchiectatic patients compared with control subjects (median [range], 1812.5 pg/ml [1226.4-4114.5 pg/ml] vs. 1342.4 pg/ml [940.3-2371.7 pg/ml]; P<0.001). There was, however, no correlation between serum TGF-beta(1) levels with FEV(1) (% predicted), FVC (% predicted), 24h sputum volume, the number of bronchiectatic lung lobes or total white blood cell count (P>0.05). Our findings support previous indications that TGF-beta(1) may contribute to bronchiectatic airway inflammation. Further studies on the potential mechanisms and pathogenesis implications of this elevation should also be pursued in future.

Clinical value of ciliary assessment in bronchiectasis.

Although ciliary dysfunction and numerous ultrastructural defects have been described, and these could be etiologically important in the development of bronchiectasis, their correlation with relevant clinical parameters have not been systematically evaluated. We have prospectively evaluated the prevalence and clinical significance of ciliary beat frequency and ultrastructural defects of nasal respiratory mucosa obtained from 152 stable patients with idiopathic bronchiectasis (100F, 57.7 +/- 15.2 yrs) and 127 control subjects (58F, 56.0 +/- 24.2 yrs). Bronchiectasis patients had significantly slower ciliary beat frequency (p < 0.05), and a greater percent of patients had central and peripheral microtubular defects (OR 14.4, 95% CI 5.6-36.8), namely, extra peripheral microtubules, "9 + 1", "8 + 2", and compound cilia (p < 0.05), but not microtubular disarrangement, extra matrix or ciliary tail abnormalities (p > 0.05), than controls. Bronchiectasis patients also had a greater proportion of cilia with any ultrastructural microtubular defects, compound cilia, and ciliary tails than controls (p < 0.05). Ciliary beat frequency did not correlate with clinically relevant parameters (p > 0.05). However, the percent of cilia with central, but not peripheral, microtubular defects correlated with 24 h sputum volume (r = 0.40, p = 0.001, and r = -0.04, p = 0.70, respectively) and FEV1 (r = -0.24, p = 0.01, and r = 0.00, p = 0.99 respectively). Our results strongly suggest a pathogenic role for central microtubular defects in the development of idiopathic bronchiectasis.

Ciliary central microtubular orientation is of no clinical significance in bronchiectasis.

It has been suggested that patients with bronchiectasis might have increased central microtubular orientation angle (CMOA), which leads to poor coordination of ciliary beating, and consequently impairment of airway defence. We have employed transmission electron microscopy to assess CMOA of ciliated nasal mucosa in a cohort of 133 (81F, 56.8+/-16.1yr) stable bronchiectasis and 59 healthy subjects (30F, 49.3+/-22.1yr). There was no significant difference in CMOA between bronchiectasis (13.2 degree) and control subjects (13.0 degree, P=0.82). There was no significant difference in CMOA among patients according to the etiology of bronchiectasis, presence of nasal symptoms, or sputum status of Pseudomonas aeruginosa infection. Patients with more severe bronchiectasis, i.e. those with FEV(1) <60%, FVC <60%, or more than 4 bronchiectatic lung lobes, had significantly lower CMOA than their counterparts (P<0.05). There was no correlation between CMOA with age, 24h sputum volume, exacerbation frequency, FEV(1), FVC, or the number of bronchiectatic lung lobes (P>0.05). CMOA correlated with ciliary beat frequency (negative), and the percent of cilia showing ultrastructural or microtubular defects (P<0.05). Central microtubular orientation angle does not correlate with clinically important parameters, in contrary to the results reported by previously published smaller scale studies.

Systemic oxidative and antioxidative status in Chinese patients with asthma.

BACKGROUND: Patients with asthma generate an increased amount of reactive oxygen species from peripheral blood cells. Reactive oxygen species produce many of the pathophysiologic changes associated with asthma and may contribute to its pathogenesis. OBJECTIVE: We investigated changes in antioxidant enzyme activities and oxidized glutathione (glutathione disulfide; GSSG) levels in erythrocytes from a group of healthy control Chinese subjects (n=135) and patients with asthma (n=106). METHODS: Baseline pulmonary function was measured for all subjects. Antioxidant status was evaluated by measuring erythrocyte superoxide dismutase, catalase, and glutathione peroxidase activities. Oxidative stress was also measured in terms of GSSG in erythrocytes with a kinetic microassay. RESULTS: Patients with asthma had significantly increased erythrocyte superoxide dismutase and catalase activities compared with controls (61.10 +/- 1.30 U/g hemoglobin [Hb] vs 55.51 +/- 1.82 U/g Hb [P=.018] and 0.0637 +/- 0.0021 U/g Hb vs 0.0257 +/- 0.0120 U/g Hb [P <.001] for the asthma and control groups, respectively). Conversely, erythrocyte glutathione peroxidase activity decreased (44.21 +/- 1.33 mU/g Hb vs 50.07 +/- 1.39 mU/g Hb for the asthma and control groups, respectively; P=.003). Patients with asthma also had significantly higher GSSG levels in erythrocyte hemolysates compared with controls (167.40 +/- 2.93 micromol/L vs 44.98 +/- 0.44 micromol/L for the asthma and control groups, respectively; P <.001), indicating increased oxidative stress. CONCLUSIONS: Asthma is accompanied by an alteration in systemic antioxidant status due to possible oxidative stress in this disease.

An indolent case of severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is a highly contagious and typically rapidly progressive form of atypical pneumonia, which spread from Asia to many parts of the world in early 2003. Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels. We report the case of a woman who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia. She presented initially with fever and a normal chest radiograph. Her indolent clinical course of SARS was punctuated by resolution of fever, but there was progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus. Treatment with oral prednisolone and ribavirin normalized her lymphopenia, altered transaminases, chest radiograph and high-resolution computed tomography appearances rapidly. Our experience should alert other clinicians in recognizing this atypical indolent presentation of SARS, to protect health care workers and the community at large and to ensure that these patients are properly treated.

Severe acute respiratory syndrome: relationship between radiologic and clinical parameters.

PURPOSE: To quantify severity of severe acute respiratory syndrome (SARS) on chest radiographs and to determine its relationship with clinical parameters. MATERIALS AND METHODS: Forty patients (mean age, 42.90 years +/- 14.01 [SD]; median age, 41.5 years; age range, 25-82 years) with clinically diagnosed SARS were evaluated. Heart rate, oxygen saturation, temperature, and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were recorded daily. Severity of lung changes on chest radiographs was scored according to percentage of involved lung. Radiographic scores at days of admission, treatment, and maximal radiographic score were extracted for statistical analysis with clinical parameters. Time to maximal radiographic score from admission and days between onset and beginning of treatment were determined. Correlations between radiographic and clinical parameters were evaluated with Spearman rank correlation. Sex differences with respect to clinical and radiographic parameters were evaluated with Mann-Whitney test. RESULTS: Median chest radiographic scores peaked 5 days after beginning of treatment before they declined. Maximal and treatment radiographic scores were inversely related to oxygen saturation (r = -0.67, P <.001; r = -0.35, P =.03). Admission radiographic score was correlated with admission AST level (r = 0.53, P =.003); treatment radiographic score, with treatment ALT and AST levels (r = 0.43, P =.007; r = 0.42, P =.019); and time to maximal radiographic score, with AST level at maximal radiographic score (r = -0.45, P =.006), admission radiographic score (r = -0.55, P <.001), treatment radiographic score (r = -0.58, P <.001), and admission ALT and AST levels (r = -0.44, P =.007; r = -0.58, P =.001). Treatment delay was associated with AST level at maximal radiographic score (r = 0.53, P =.001), treatment radiographic score (r = 0.60, P <.001), and time to maximal radiographic score (r = -0.36, P =.02). No sex differences occurred with respect to radiographic and clinical parameters (P >.05). CONCLUSION: Severity of lung abnormalities quantified on chest radiographs correlates with clinical and laboratory parameters.

Silicosis in 76 men: qualitative and quantitative CT evaluation--clinical-radiologic correlation study.

PURPOSE: To use qualitative and quantitative computed tomography (CT) to test the hypothesis that impaired lung function with silicosis is due to progressive massive fibrosis (PMF) and associated emphysema. MATERIALS AND METHODS: Seventy-six men with silicosis underwent volumetric and thin-section CT of the thorax. Lung function, Borg scale dyspnea grade, silica exposure duration, and cigarette consumption were determined. Nodular profusion (NP) at chest radiography was graded according to the International Labor Organization radiographic classification system; NP and PMF at CT were visually graded by using five-point (ie, grades 0-4) and four-point (grades 0-3) scales, respectively. Emphysema and NP, which together are defined as the NP index, were quantified by using attenuation threshold values of less than -950 HU and greater than -100 HU, respectively. Mean lung attenuation was also determined. Relationships among the CT, chest radiographic, and clinical parameters were analyzed by using Spearman correlation. RESULTS: NP at chest radiography correlated (r > 0.50) with all CT parameters of nodularity. CT PMF had the highest correlation with emphysema (r = 0.58, P <.001). NP at chest radiography and all CT parameters were inversely related to lung function. At multiple regression analysis, PMF and emphysema index (both at CT) were significant determinants of forced expiratory volume in 1 second (FEV1) (P =.006 and.03, respectively) and FEV1 to forced vital capacity (FVC) ratio (P =.007 and.02, respectively). Mean lung attenuation remained related to FVC (P =.03), diffusing capacity of lung for carbon monoxide (P =.04), and Borg scale grade (P =.01). Cigarette consumption and silica exposure duration had no independent effects on lung function. CONCLUSION: Qualitative and quantitative CT parameters can be used as indirect measures of functional impairment in silicosis. PMF and emphysema are independently related to airflow obstruction, whereas mean lung attenuation is related to clinical dyspnea and reduced lung volume.

High-dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome.

The treatment of atypical pneumonia, subsequently termed severe acute respiratory syndrome (SARS), is controversial, and the efficacy of corticosteroid therapy is unknown. We have evaluated the clinical and radiographic outcomes of 72 patients with probable SARS (median age 37 years, 30 M), who received ribavirin and different steroid regimens in two regional hospitals. Chest radiographs were scored according to the percentage of lung field involved. Seventeen patients initially received pulse steroid (PS) (methylprednisolone > or =500 mg/day) and 55 patients initially received nonpulse steroid (NPS) (methylprednisolone <500 mg/day) therapy. The cumulative steroid dosage; intensive care unit admission, mechanical ventilation, and mortality rates; and hematologic and biochemical parameters were similar in both groups after 21 days. However, patients in the PS group had less oxygen requirement, better radiographic outcome, and less likelihood of requiring rescue PS therapy than their counterparts. There was no significant difference between the two groups in hemolytic anemia, severe secondary infections, or hematemesis, but patients in the PS group had less hyperglycaemia. Initial use of pulse methylprednisolone therapy appears to be a more efficacious and an equally safe steroid regimen when compared with regimens with lower dosage and should be considered as the preferred steroid regimen in the treatment of SARS, pending data from future randomized controlled trials.

A cluster of cases of severe acute respiratory syndrome in Hong Kong.

BACKGROUND: Information on the clinical features of the severe acute respiratory syndrome (SARS) will be of value to physicians caring for patients suspected of having this disorder. METHODS: We abstracted data on the clinical presentation and course of disease in 10 epidemiologically linked Chinese patients (5 men and 5 women 38 to 72 years old) in whom SARS was diagnosed between February 22, 2003, and March 22, 2003, at our hospitals in Hong Kong, China. RESULTS: Exposure between the source patient and subsequent patients ranged from minimal to that between patient and health care provider. The incubation period ranged from 2 to 11 days. All patients presented with fever (temperature, >38 degrees C for over 24 hours), and most presented with rigor, dry cough, dyspnea, malaise, headache, and hypoxemia. Physical examination of the chest revealed crackles and percussion dullness. Lymphopenia was observed in nine patients, and most patients had mildly elevated aminotransferase levels but normal serum creatinine levels. Serial chest radiographs showed progressive air-space disease. Two patients died of progressive respiratory failure; histologic analysis of their lungs showed diffuse alveolar damage. There was no evidence of infection by Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophila. All patients received corticosteroid and ribavirin therapy a mean (+/-SD) of 9.6+/-5.42 days after the onset of symptoms, and eight were treated earlier with a combination of beta-lactams and macrolide for 4+/-1.9 days, with no clinical or radiologic efficacy. CONCLUSIONS: SARS appears to be infectious in origin. Fever followed by rapidly progressive respiratory compromise is the key complex of signs and symptoms from which the syndrome derives its name. The microbiologic origins of SARS remain unclear.

Extrapulmonary presentation of asymptomatic pulmonary lymphangioleiomyomatosis.

Lymphangioleiomyomatosis (LAM) is a rare parenchymal lung disease, which affects young women of childbearing age and is characterized pathologically by proliferation of interstitial smooth muscle and formation of cysts in the lung. While LAM is usually predominantly a respiratory disorder, it can also initially involve other extrapulmonary organs. We report the case of a 35-year-old Chinese woman, who presented with a 4-week history of left thigh swelling which was found to be secondary to compression of pelvic veins by a mass lesion. The latter was found histologically to show LAM. Despite the patient being asymptomatic and displaying normal lung function, a thoracic high resolution CT scan showed typical features of early LAM. This case further illustrates that LAM can have multisystem involvement, and demonstrates the importance of being aware of the diagnosis in cases presenting with extrapulmonary manifestation, in order that patients are diagnosed and managed appropriately.

High-resolution CT quantification of bronchiectasis: clinical and functional correlation.

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 (FEV(1)), ratio of FEV(1) 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 FEV(1) (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 FEV(1)/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.