An index of the fractal characteristic of an airway tree is associated with airflow limitations and future body mass index reduction in COPD patients.

Disorders of the fractality of an airway tree and a vessel tree have been studied in pulmonary diseases. Here we successfully applied Mishima's D to the bronchial minimal inner cross-sectional area (iCSA) measured in multidetector computed tomography (MDCT) images of chronic obstructive pulmonary disease (COPD) and non-COPD smokers (n = 162), by defining D in the following formula: logN(≥X) = -D × logX + c, where X is a certain iCSA value, N(≥X) is the number of airway branches having iCSA greater than or equal to X, and c is a constant. Mathematically, this D of iCSA was associated with the expected reduction ratio of iCSA at bifurcations, which can be estimated by 2-1/D. This D of iCSA also correlated weakly with the box-counting fractal dimension and Weibel's reduction ratio over airway generations, which indicated that the airway tree was not a perfect fractal object and that the branch bifurcation was asymmetric. The D of iCSA showed positive correlations with lung function measurements of airflow limitation in study participants. In addition, D of iCSA representing the periphery showed an association with future body mass index reduction, most likely as an indicator of energy efficacy for breathing as predicted by Hess-Murray's law. D of iCSA may be helpful to understanding the pathogenesis of obstructive lung diseases.NEW & NOTEWORTHY An airway tree is a fractal object. We showed that the distribution of minimal inner cross-sectional area (iCSA) of airway branches can be expressed by a fractal index, D, of minimal iCSA. This D was correlated with airflow limitation and future body mass index reduction in chronic obstructive pulmonary disease patients, as predicted by Hess-Murray's law.

Computed tomography (CT)-assessed bronchodilation induced by inhaled indacaterol and glycopyrronium/indacaterol in COPD.

BACKGROUND: Our previous studies suggested that the site of bronchodilation on CT might differ between inhaled ß2 agonists and inhaled anticholinergics in COPD. AIM: To assess and compare the bronchodilation effects of inhaled indacaterol and glycopyrronium/indacaterol by airway generation in large airways using CT. METHODS: CT scans at full inspiration and pulmonary function tests were done in 25 patients with moderate-severe COPD before and 4-5 weeks after daily inhalation of indacaterol and again another 4-5 weeks after inhalation of glycopyrronium/indacaterol. Airway inner luminal area (Ai) at the 3rd (segmental) to 6th generation of 8 selected bronchi, a total of 32 sites, in the right lung was analyzed on 3 occasions. Our proprietary software enables us to select the same airways and the same measurement sites for comparison, with simultaneous confirmation using two screens on the computer. RESULTS: The overall increase of Ai (ΔAi, %) averaged at all 32 measurement sites induced by glycopyrronium/indacaterol had a significant correlation with FEV1 improvement (r = 0.7466, p < 0.0001). Both ΔAi, % with indacaterol and ΔAi, % with additional glycopyrronium were significant at the 3rd to 6th generations. Remarkable increases in ΔAi, % were found at the 5th and 6th generations in several subjects with indacaterol or additional glycopyrronium. There were no significant site-differences in the bronchodilation pattern caused by indacaterol and by glycopyrronium/indacaterol at any of the 3rd to 6th generations. CONCLUSIONS: Additional bronchodilation with glycopyrronium was demonstrated by CT at the 3rd to 6th generations, with no site-specific differences in bronchodilation between indacaterol and glycopyrronium/indacaterol. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) system (http://www.umin.ac.jp/. ID. UMIN000012043).

Increased Epicardial Adipose Tissue Is Associated with the Airway Dominant Phenotype of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Epicardial adipose tissue (EAT) has been shown to be a non-invasive marker that predicts the progression of cardiovascular disease (CVD). It has been reported that the EAT volume is increased in patients with chronic obstructive pulmonary disease (COPD). However, little is known about which phenotypes of COPD are associated with increased EAT. METHODS: One hundred and eighty smokers who were referred to the clinic were consecutively enrolled. A chest CT was used for the quantification of the emphysematous lesions, airway lesions, and EAT. These lesions were assessed as the percentage of low attenuation volume (LAV%), the square root of airway wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10) and the EAT area, respectively. The same measurements were made on 225 Vietnamese COPD patients to replicate the results. RESULTS: Twenty-six of the referred patients did not have COPD, while 105 were diagnosed as having COPD based on a FEV1/FVC<0.70. The EAT area was significantly associated with age, BMI, FEV1 (%predicted), FEV1/FVC, self-reported hypertension, self-reported CVD, statin use, LAV%, and √Aaw at Pi10 in COPD patients. The multiple regression analyses showed that only BMI, self-reported CVD and √Aaw at Pi10 were independently associated with the EAT area (R2 = 0.51, p<0.0001). These results were replicated in the Vietnamese population. CONCLUSIONS: The EAT area is independently associated with airway wall thickness. Because EAT is also an independent predictor of CVD risk, these data suggest a mechanistic link between the airway predominant form of COPD and CVD.

A mixed phenotype of airway wall thickening and emphysema is associated with dyspnea and hospitalization for chronic obstructive pulmonary disease.

RATIONALE: Quantitative computed tomography (CT) has been used to phenotype patients with chronic obstructive pulmonary disease (COPD). A mixed phenotype is defined as the presence of both airway wall thickening and emphysema on quantitative CT. Little is known about patients with COPD with the mixed phenotype. OBJECTIVES: To propose a method of phenotyping COPD based on quantitative CT and to compare clinically relevant outcomes between patients with COPD with the mixed phenotype and those with other CT-based phenotypes. METHODS: Each of 427 male smokers (187 without COPD, 240 with COPD) underwent a complete medical interview, pulmonary function testing, and whole-lung CT on the same day. The percentage of low-attenuation volume at the threshold of -950 Hounsfield units (%LAV) and the square root of wall area of a hypothetical airway with an internal perimeter of 10 mm (Pi10) were measured. Patients with COPD were classified into four distinct phenotypes based on the upper limits of normal for %LAV and Pi10, which were derived from the data of smokers without COPD by using quantile regression. MEASUREMENTS AND MAIN RESULTS: Of 240 patients with COPD, 52 (21.7%) were classified as CT-normal phenotype, 39 (16.3%) as airway-dominant phenotype, 103 (42.9%) as emphysema-dominant phenotype, and 46 (19.2%) as mixed phenotype. Patients with COPD with the mixed phenotype were associated with more severe dyspnea than those with each of the remaining CT-based phenotypes (P < 0.01 for all comparisons). The number of hospitalizations for COPD exacerbations during the preceding year was 2.0 to 3.6 times higher in patients with the mixed phenotype than in those with each of the remaining CT-based phenotypes (P < 0.05 for all comparisons). Findings persisted after adjustment for age, pack-years of smoking, smoking status, body mass index, and FEV1. CONCLUSIONS: Patients with COPD with the mixed phenotype are associated with more severe dyspnea and more frequent hospitalizations than those with each of the remaining CT-based phenotypes. Thus, patients with COPD with the mixed phenotype may need more attention and interventions.

Mediastinitis and pericarditis after endobronchial ultrasound-guided transbronchial needle aspiration.

A 73-year-old man was admitted to our hospital for further investigation of multiple lung nodules and lymphadenopathy that were observed on chest radiography. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was performed to sample the lower paratracheal lymph node (4R), leading to a definitive diagnosis of squamous cell carcinoma of the lung. About 2 weeks after EBUS-TBNA, the patient had a high temperature, anterior chest pain, tachycardia, and hypotension. The diagnosis of infectious mediastinitis and pericarditis as complications of EBUS-TBNA, which were successfully treated with systemic antibiotics, was made after examinations. EBUS-TBNA is minimally invasive and useful for the diagnosis of hilar and mediastinum lesions particularly in determining the extent of lung cancer. With the increased employment of this method, critical complications may also increase. Clinicians should be aware of the rare but critical complications associated with EBUS-TBNA.

Airway wall area derived from 3-dimensional computed tomography analysis differs among lung lobes in male smokers.

BACKGROUND: It is time-consuming to obtain the square root of airway wall area of the hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), a comparable index of airway dimensions in chronic obstructive pulmonary disease (COPD), from all airways of the whole lungs using 3-dimensional computed tomography (CT) analysis. We hypothesized that √Aaw at Pi10 differs among the five lung lobes and √Aaw at Pi10 derived from one certain lung lobe has a high level of agreement with that derived from the whole lungs in smokers. METHODS: Pulmonary function tests and chest volumetric CTs were performed in 157 male smokers (102 COPD, 55 non-COPD). All visible bronchial segments from the 3rd to 5th generations were segmented and measured using commercially available 3-dimensional CT analysis software. √Aaw at Pi10 of each lung lobe was estimated from all measurable bronchial segments of that lobe. RESULTS: Using a mixed-effects model, √Aaw at Pi10 differed significantly among the five lung lobes (R(2) = 0.78, P<0.0001). The Bland-Altman plots show that √Aaw at Pi10 derived from the right or left upper lobe had a high level of agreement with that derived from the whole lungs, while √Aaw at Pi10 derived from the right or left lower lobe did not. CONCLUSION: In male smokers, CT-derived airway wall area differs among the five lung lobes, and airway wall area derived from the right or left upper lobe is representative of the whole lungs.

[A case of tuberculosis that occurred during treatment of hepatocellular carcinoma with sorafenib].

A 66-year-old man with hepatocellular carcinoma (HCC) and suspicion of lung metastasis consulted us because of an abnormal chest shadow as seen on a radiograph. He had been treated with sorafenib for 2 months. A chest CT scan showed cavitating nodules in the left upper lobe that were present before therapy with sorafenib, and infiltrative shadows in the subpleural areas of the right upper lobe. The shadows were diagnosed, at least in part, as pulmonary tuberculosis by using a nucleic acid amplification test for Mycobacterium tuberculosis in the sputum that yielded a positive result. Treatment with antituberculosis drugs resulted in a good clinical response. However, the patient died of HCC. We concluded that the nodule in the right upper lobe was old pulmonary tuberculosis, because it did not change during the course of the disease and because the cavities in the left upper lobe were active lesions. Sorafenib is a molecularly targeted agent that has been proven effective for treating advanced HCC with extrahepatic metastasis. It may also cause necrosis within lung metastases as an anti-tumor effect. Therefore, pulmonary tuberculosis, including reactivation, should be considered in the differential diagnosis when treating a patient with sorafenib.

Respiratory failure of Williams-Campbell syndrome is effectively treated by noninvasive positive pressure ventilation.

Williams-Campbell syndrome is a rare disease, characterized by a congenital deficiency of cartilage in the fourth to sixth order bronchi, leading to chronic respiratory failure with recurrent pulmonary infections. An effective and practical treatment has not yet been established. A 31-year-old man who was diagnosed as Williams-Campbell syndrome by inspiratory and expiratory computed tomography findings developed recurrent pulmonary infections and showed progressive deterioration of dyspnea. Domiciliary NPPV was administered, followed by a dramatic improvement of respiratory failure and a decrease in the episodes of pulmonary infections. NPPV may have an advantage in adults with Williams-Campbell syndrome who have severe respiratory failure and recurrent pulmonary infections.

Diffuse alveolar haemorrhage may be associated with intravitreal injection of bevacizumab in a patient with systemic risk factors.

The authors present a rare case where acute respiratory failure occurred after the intravitreal bevacizumab injection for a branch retinal vein occlusion. Chest CT scan showed ground-glass opacity in the bilateral lung fields. The finding of bronchoalveolar lavage fluid revealed alveolar haemorrhage. Corticosteroid therapy resulted in a rapid improvement of respiratory failure. This report suggests that intravitreal injection of bevacizumab may be associated with diffuse alveolar haemorrhage and acute lung injury.