Quantitative computed tomography-derived clusters: redefining airway remodeling in asthmatic patients.

BACKGROUND: Asthma heterogeneity is multidimensional and requires additional tools to unravel its complexity. Computed tomography (CT)-assessed proximal airway remodeling and air trapping in asthmatic patients might provide new insights into underlying disease mechanisms. OBJECTIVES: The aim of this study was to explore novel, quantitative, CT-determined asthma phenotypes. METHODS: Sixty-five asthmatic patients and 30 healthy subjects underwent detailed clinical, physiologic characterization and quantitative CT analysis. Factor and cluster analysis techniques were used to determine 3 novel, quantitative, CT-based asthma phenotypes. RESULTS: Patients with severe and mild-to-moderate asthma demonstrated smaller mean right upper lobe apical segmental bronchus (RB1) lumen volume (LV) in comparison with healthy control subjects (272.3 mm(3) [SD, 112.6 mm(3)], 259.0 mm(3) [SD, 53.3 mm(3)], 366.4 mm(3) [SD, 195.3 mm(3)], respectively; P = .007) but no difference in RB1 wall volume (WV). Air trapping measured based on mean lung density expiratory/inspiratory ratio was greater in patients with severe and mild-to-moderate asthma compared with that seen in healthy control subjects (0.861 [SD, 0.05)], 0.866 [SD, 0.07], and 0.830 [SD, 0.06], respectively; P = .04). The fractal dimension of the segmented airway tree was less in asthmatic patients compared with that seen in control subjects (P = .007). Three novel, quantitative, CT-based asthma clusters were identified, all of which demonstrated air trapping. Cluster 1 demonstrates increased RB1 WV and RB1 LV but decreased RB1 percentage WV. On the contrary, cluster 3 subjects have the smallest RB1 WV and LV values but the highest RB1 percentage WV values. There is a lack of proximal airway remodeling in cluster 2 subjects. CONCLUSIONS: Quantitative CT analysis provides a new perspective in asthma phenotyping, which might prove useful in patient selection for novel therapies.

Quantitative analysis of high-resolution computed tomography scans in severe asthma subphenotypes.

BACKGROUND: Severe asthma is a heterogeneous condition. Airway remodelling is a feature of severe asthma and can be determined by the assessment of high-resolution computed tomography (HRCT) scans. The aim of this study was to assess whether airway remodelling is restricted to specific subphenotypes of severe asthma. METHODS: A retrospective analysis was performed of HRCT scans from subjects who had attended a single-centre severe asthma clinic between 2003 and 2008. The right upper lobe apical segmental bronchus (RB1) dimensions were measured and the clinical and sputum inflammatory characteristics associated with RB1 geometry were assessed by univariate and multivariate regression analyses. Longitudinal sputum data were available and were described as area under the time curve (AUC). Comparisons were made in RB1 geometry across subjects in four subphenotypes determined by cluster analysis, smokers and non-smokers, and subjects with and without persistent airflow obstruction. RESULTS: Ninety-nine subjects with severe asthma and 16 healthy controls were recruited. In the subjects with severe asthma the RB1 percentage wall area (%WA) was increased (p=0.009) and lumen area (LA)/body surface area (BSA) was decreased (p=0.008) compared with controls but was not different across the four subphenotypes. Airway geometry was not different between smokers and non-smokers and RB1 %WA was increased in those with persistent airflow obstruction. RB1 %WA in severe asthma was best associated with airflow limitation and persistent neutrophilic airway inflammation (model R(2)=0.27, p=0.001). CONCLUSIONS: Airway remodelling of proximal airways occurs in severe asthma and is associated with impaired lung function and neutrophilic airway inflammation.

Thoracic ultrasound prior to medical thoracoscopy improves pleural access and predicts fibrous septation.

BACKGROUND AND OBJECTIVE: Medical thoracoscopy (MT) is indicated for the investigation of unexplained pleural exudates. Not all MT units create artificial pneumothoraces because of time. Difficult pleural space access and thick fibrous adhesions may prevent MT and pleurodesis, respectively. The potential role of thoracic ultrasound (TUS) pre-MT has not been fully evaluated. We hypothesized TUS would reduce failure to access the pleural space and enable detection of thick fibrous adhesions. METHODS: Thirty patients underwent single port MT consecutively for investigation of pleural exudates without pre-MT TUS over a 6-month period. Over the following 6 months, 30 consecutive patients underwent TUS immediately prior to MT. Pleural access rate and thick fibrous adhesion detection at both MT and TUS were recorded. RESULTS: In the non-TUS cohort, pleural space access failure occurred in 16.7% (leading to five extra procedures), versus no failures in the TUS cohort (P = 0.0522). There were no differences in prevalence of MT fibrous adhesions between cohorts. TUS identified all cases of fibrous septation versus only 12.5% identified by CT in the non-TUS cohort (P = 0.001). All identified cases of thick fibrous septation on TUS did not receive pleurodesis at MT. TUS detected useful ancillary features in 43% of cases. CONCLUSIONS: A strong trend to reduction in single port MT pleural access failure was noted with pre-MT TUS thus reducing extra procedures and the need for artificial pneumothoraces. Pre-MT TUS also reliably detects thick fibrous adhesions at MT. TUS may also detect useful ancillary features. This study provides a rationale for ultrasound-guided single port MT if a pneumothorax is not created.

Pseudo tumors of the lung after lung volume reduction surgery.

We describe 2 patients who underwent lung volume reduction surgery, who postoperatively had computed tomographic scans that showed symptomatic mass lesions suggestive of malignancy and an inhaled foreign body. Investigations excluded these conditions with the remaining likely diagnosis of pseudotumor secondary to buttressing material. These potential sequelae of lung volume reduction surgery should be recognized in follow-up investigations.

The Role of Multi Detector Computed Tomographic Imaging Prior to Clinic Consultation in Patients Suspected to Have Lung Cancer.

BACKGROUND: Scanning patients early in their diagnostic journey helps in differentiating benign from malignant aetiology. There is increasing pressure on diagnostic practices for rapid diagnoses and thereby early commencement of treatment in patients suspected to have lung cancer (LC). In our practice, multi detector computed tomography (MDCT) imaging is performed in selected patients referred to the LC service prior to them seeing a chest physician in the LC clinic. This study evaluates the role of such practice and reviews its potential impact on LC services. METHODS: Prospective review of our practice from January 2007 to Apr 2007 was performed. Consecutive patients referred to the service with suspected LC were included. Chest radiograph (CXR) report and clinical information from general practitioners were reviewed and graded as high, medium or low risk for presence of LC. Patients with sufficient clinical and/or radiological concern underwent MDCT imaging prior to their clinic. Combined risk scores and modified risk scores were formulated and assessed against MDCT findings. RESULTS: A total of 139 patients were referred to the service, 124 of these had pre-clinic MDCT. Fifty-three patients (43%) had malignancy, 39 (31%) had non-malignant significant abnormalities, 17 (14%) had other incidental findings and 15 (12%) were normal. Modified combined risk score was the best predictor of presence of cancer. CONCLUSION: Pre-clinic MDCT scanning in patients with suspected LC is feasible and has a promising role in the modern care of LC patients. It also empowers physicians with additional information at the primary consultation.

Implications of new (seventh) TNM classification of lung cancer on general radiologists--a pictorial review.

The new TNM (seventh) classification of lung cancer, published by Union Internationale Centre le Cancer, has been in use since January 2010. It is vital for general radiologists to be well versed with this system and be aware of the impact of these changes on patient management and prognosis. It is also important that radiologists appreciate the implications of the new system on reporting different imaging modalities and its limitations. This pictorial essay outlines the proposed changes, its limitations, and implications for radiologists.

The role of CT scanning in multidimensional phenotyping of COPD.

BACKGROUND: COPD is a heterogeneous disease characterized by airflow obstruction and diagnosed by lung function. CT imaging is emerging as an important, noninvasive tool in phenotyping COPD. However, the use of CT imaging in defining the disease heterogeneity above lung function is not fully known. METHODS: Seventy-five patients with COPD (58 men, 17 women) were studied with CT imaging and with measures of airway inflammation. Airway physiology and health status were also determined. RESULTS: The presence of emphysema (EM), bronchiectasis (BE), and bronchial wall thickening (BWT) was found in 67%, 27%, and 27% of subjects, respectively. The presence of EM was associated with lower lung function (mean difference % FEV(1), -20%; 95% CI, -28 to -11; P < .001). There was no difference in airway inflammation, exacerbation frequency, or bacterial load in patients with EM alone or with BE and/or BWT ± EM. The diffusing capacity of the lung for carbon monoxide/alveolar volume ratio was the most sensitive and specific parameter in identifying EM (area under the receiver operator characteristic curve, 0.87; 95% CI, 0.79-0.96). Physiologic cluster analysis identified three clusters, two of which were EM predominant and the third characterized by a heterogeneous combination of EM and BE. CONCLUSIONS: The application of CT imaging can be useful as a tool in the multidimensional approach to phenotyping patients with COPD.

Qualitative analysis of high-resolution CT scans in severe asthma.

BACKGROUND: High-resolution CT (HRCT) scanning is part of the management of severe asthma, but its application varies between centers. We sought to describe the HRCT scan abnormalities of a large severe asthma cohort and to determine the utility of clinical features to direct the use of HRCT scanning in this group of patients. METHODS: Subjects attending our Difficult Asthma Clinic (DAC) between February 2000 and November 2006 (n = 463) were extensively re-characterized and 185 underwent HRCT scan. The HRCT scans were analyzed qualitatively and the interobserver variability was assessed. Using logistic regression we defined clinical parameters that were associated with bronchiectasis (BE) and bronchial wall thickening (BWT) alone or in combination. RESULTS: HRCT scan abnormalities were present in 80% of subjects and often coexisted with BWT (62%), BE (40%), and emphysema (8%). The interobserver agreement for BE (kappa = 0.76) and BWT (kappa = 0.63) was substantial. DAC patients who underwent HRCT scanning compared with those who did not were older, had longer disease duration, had poorer lung function, were receiving higher doses of corticosteroids, and had increased neutrophilic airway inflammation. The sensitivity and specificity of detecting BE clinically were 74% and 45%, respectively. FEV(1)/FVC ratio emerged as an important predictor for both BE and BWT but had poor discriminatory utility for subjects who did not have airway structural changes (FEV(1)/FVC ratio, >or= 75%; sensitivity, 67%; specificity, 65%). CONCLUSION: HRCT scan abnormalities are common in patients with severe asthma. Nonradiologic assessments fail to reliably predict important bronchial wall changes; therefore, CT scan acquisition may be required in all patients with severe asthma.

Clinical, radiologic, and induced sputum features of chronic obstructive pulmonary disease in nonsmokers: a descriptive study.

Epidemiologic studies show that 5-12% of subjects with chronic obstructive pulmonary disease (COPD) are nonsmokers. Little is known about the pathophysiology of the fixed airflow obstruction in these subjects. We have prospectively identified 25 patients with COPD who had never smoked or had a less than 5 pack years smoking history and present the clinical, radiologic, and induced sputum features. Our population represented 5.7% of total referrals with fixed airflow obstruction over 2 years. Patients had a mean age of 70 years, were predominantly female (86%), and had a mean duration of respiratory symptoms of 7 years. The mean FEV(1) was 58%, and the FEV(1)/FVC was 55%. Features on high-resolution computed tomographic scanning were nonspecific and were considered typical of a wider population with COPD. An induced sputum differential inflammatory cell count suggested the presence of two distinct groups. Nine had significant sputum eosinophilia (mean, 8.1%; normal, less than 1.9%), and the remaining 13 had a normal sputum eosinophil and tended to have a raised sputum neutrophil count (mean, 70.1%; normal, less than 65%). Organ-specific autoimmune disease was present in 7 of the 22 patients (32%) and was particularly prevalent in those without sputum eosinophilia (6 of 13). In conclusion, COPD in nonsmokers predominantly affects females and has at least two pathologic subgroups, one of which may be associated with organ-specific autoimmune disease. Further investigation of this group may disclose novel mechanisms of fixed airflow obstruction.