[Esophagectomy for Bronchogenic Cyst within the Esophageal Muscle Layer with Dysphagia:Report of a Case].

A 26-year-old man referred to our hospital because of dysphagia and a mediastinal tumor detected on chest computed tomography (CT). A contrast-enhanced CT revealed a 12 cm long cystic tumor along the right thoracic esophagus. An upper gastrointestinal endoscopy showed no abnormalities in the esophageal mucosa, and an unclear boundary between the tumor and the esophageal wall was observed by echography. In surgery, the tumor and the esophagus were in one lump, and esophagectomy was performed. On the fourth postoperative day, esophagogastric anastomosis was performed with poststernal reconstruction, and the patient was discharged home on the 38th postoperative day. Pathological examination revealed that the mass was a cystic lesion within the esophageal muscular layer, and the cyst wall was coated with airway-like multi-lineal hairy epithelium, which led to the diagnosis of a bronchogenic cyst. Even if the cyst is within the esophageal muscularis layer, bronchogenic cyst should be considered in the differential.

[Pulmonary Herniation Requiring Reconstructive Surgery Caused by Minimally Invasive Cardiac Surgery:Report of a Case].

A 72-year-old man who underwent aortic valve replacement by a minimally invasive cardiac surgery (MICS) approach two years ago was visited our hospital complaining of swelling and pain in the right anterior chest. A chest computed tomography (CT) scan showed that the right upper lobe protruded beyond the right second intercostal space and outside the thorax. He was diagnosed as a right intercostal lung hernia and underwent chest wall reconstruction with a substitute method. Postoperative course was uneventful without any evidence of recurrence. Postoperative intercostal lung hernias in MICS may increase with the increment in MICS, and it is necessary to accumulate cases as one of the complications.

An Analytical Model for Estimating Alveolar Wall Elastic Moduli From Lung Tissue Uniaxial Stress-Strain Curves.

The non-linear stress-strain behavior of uniaxially-stretched lung parenchyma is thought to be an emergent phenomenon arising from the ensemble behavior of its microscopic constituents. Such behavior includes the alignment and elongation of randomly oriented alveolar walls with initially flaccid fibers in the direction of strain. To account for the link between microscopic wall behavior and the macroscopic stress-strain curve, we developed an analytical model that represents both alignment and elongation of alveolar walls during uniaxial stretching. The model includes the kinetics and mechanical behavior of randomly oriented elastic alveolar walls that have a bending stiffness at their intersections. The alignment and stretch of the walls following incremental stretch of the tissue were determined based on energy minimization, and the total stress was obtained by differentiating the total energy density with respect to strain. The stress-strain curves predicted by the model were comparable to curves generated by a previously published numerical alveolar network model. The model was also fit to experimentally measured stress-strain curves in parenchymal strips obtained from mice with decreased lung collagen content, and from young and aged mice. This yielded estimates for the elastic modulus of an alveolar wall, which increased with age from 4.4 to 5.9 kPa (p = 0.043), and for the elastic modulus of fibers within the wall, which increased with age from 311 to 620 kPa (p = 0.001). This demonstrates the possibility of estimating alveolar wall mechanical properties in biological soft tissue from its macroscopic behavior given appropriate assumptions about tissue structure.

Non-small cell lung cancer with pathological complete response: predictive factors and surgical outcomes.

OBJECTIVES: When induction therapy followed by surgery for locally advanced non-small cell lung cancer results in pathological complete response, the prognosis is excellent; however, relapses can occur. We analyzed the predictive factors for achieving pathological complete response and reviewed the clinicopathological features and surgical outcomes of locally advanced non-small cell lung cancer with pathological complete response. METHODS: Between March 2005 and January 2015, 145 resections after induction therapy for locally advanced non-small cell lung cancer were performed; 38 cases achieved pathological complete response. Predictive factors for achieving pathological complete response were analyzed, and the clinicopathological features and surgical outcomes of 38 cases with pathological complete response were retrospectively reviewed. RESULTS: Of 145 patients, 98 underwent induction chemoradiation and 47, induction chemotherapy. Squamous cell carcinoma occurred most frequently (n = 64), followed by adenocarcinoma (n = 53). Only squamous cell carcinoma was positively associated with achieving pathological complete response (p = 0.009). Of 38 patients with pathological complete response, 33 were men and the mean age was 67.0 ± 6.3 years; the clinical stages were IIA (n = 3), IIB (n = 2), IIIA (n = 26), and IIIB (n = 3). One patient died within 30 days post-surgery (2.6%). Eight recurrences occurred during the follow-up period; brain metastasis occurred most frequently. The 5-year overall and recurrence-free survival rates were 79.5% and 72.6%, respectively. CONCLUSIONS: Squamous cell carcinoma was identified as a positive predictive factor for achieving pathological complete response. Among patients undergoing lung cancer surgery after induction therapy with pathological complete response, brain metastasis occurred most frequently.

Comparing Part-Solid and Pure-Solid Tumors in the TNM Classification of Lung Cancer (Eighth Edition).

BACKGROUND: In the eighth edition of the TNM classification, the lung tumors that have the same solid components are categorized either as part-solid or pure-solid tumors. However, this is debatable since the tumors in the same T component categories were evaluated without considering this categorization, and was based on a more malignant behavior and a poorer prognosis of pure-solid tumors. The aim of this study was to investigate and compare the prognosis between part-solid and pure-solid tumors. METHODS: We retrospectively analyzed 530 patients who were diagnosed with clinical-T1a-cN0M0 non-small-cell lung cancer (NSCLC) and were treated surgically. The subjects were divided into part-solid and pure-solid tumor groups using thin-section computed tomography. The prognosis was compared between the groups. RESULTS: Although relapse-free survival (RFS) was significantly shorter in the pure-solid tumor group (p = 0.016), no significant differences were observed in the overall survival (OS) between the two groups (p = 0.247). In 137 propensity score-matched pairs, including variables such as age, gender, Brinkman index, body mass index, forced expiratory volume in 1 second/forced vital capacity, Charlson comorbidity index, carcinoembryonic antigen levels, clinical-T status, surgical procedure, and extent of surgery, no significant differences were seen in the RFS and OS between the two groups (p = 0.709 and p = 0.517, respectively). CONCLUSION: In the eighth edition of the TNM classification of clinical-T1a-cN0M0 NSCLC, the prognosis of part-solid and pure-solid tumors showed no significant differences. Solid component size of the tumor is considered important prognostic factor in early-stage NSCLC.

[Induction Chemoradiotherapy Followed by Surgery in Non-small-cell Lung Cancer;a Retrospective Study].

OBJECTIVE: The aim of this study is to investigate the outcomes of induction chemoradiotherapy (ICRT) followed by surgery in patients with non-small cell lung cancer( NSCLC). METHODS: We retrospectively analyzed consecutive patients with NSCLC who underwent ICRT followed by surgery at our hospital between January 2006 and December 2015. RESULTS: A total of 102 patients were eligible for evaluation (cStage/I B/II A/II B/III A/III B, 1/8/14/75/4). The median age was 66 years. Forty-one patients had adenocarcinoma, 42 patients had squamous cell carcinoma, and 19 patients had others. The regimen consisted of carboplatin and paclitaxel in 94 patients, and the others in 8 patients plus concurrent radiation at a dose of 28 Gy in 1 patient, 30 Gy in 28 patients, 40 Gy in 42 patients, 45 Gy in 3 patients, and 50 Gy in 28 patients. Major response was obtained in 84 patients. Grade 3/4 toxicity of ICRT reported in 57 patients. The 5-year relapse-free and overall survival rate was 51.4% and 62.7%, respectively. CONCLUSION: ICRT (carboplatin and paclitaxel plus concurrent standard radiation) followed by surgery in NSCLC can be safely performed and may contribute to satisfactory outcomes in locally advanced NSCLC. It is likely that 28~50 Gy radiation dose contributes to satisfactory outcomes in ICRT.

Surgical outcomes and complications of pneumonectomy after induction therapy for non-small cell lung cancer.

OBJECTIVES: Although surgical resection after induction therapy (IT) for locally advanced non-small cell lung cancer (NSCLC) is a possible treatment option, pneumonectomy may be avoided owing to high-surgical risks. However, reports exist that pneumonectomy after IT has acceptable safety and favorable outcomes. We reviewed pneumonectomies after IT in terms of surgical outcomes, perioperative management, and complications. METHODS: Between April 2004 and March 2015, 15 consecutive pneumonectomies were performed for locally advanced NSCLC after IT. Surgical outcomes, perioperative management, and complications were retrospectively reviewed. RESULTS: Thirteen patients were men, and 6 pneumonectomies were right-sided. One pneumonectomy was performed after induction chemotherapy and 14 followed induction chemoradiation. In all 15 cases the bronchial stumps were covered with autologous tissues. Pedunculated mediastinal fat pad and pedunculated intercostal muscles were used in 4 and 11 cases, respectively. Although postoperative complications were seen in 12 patients (80.0%), with major complications (Clavien-Dindo classification ≥ IIIa) in 5 patients (33.3%), there were no deaths within 30 days after pneumonectomy. Overall 3- and 5-year survivals were 80.0 and 57.1%, respectively. CONCLUSIONS: Owing to high-surgical risks and complication rates, careful surgical technique and postoperative management are essential for successful pneumonectomy after IT.

Expansion Thoracoplasty in Rabbit Model: Effect of Timing on Preserving Pulmonary Growth and Correcting Spine Deformity.

STUDY DESIGN: In a treatment-control animal study expansion thoracoplasty (ET) was performed in a juvenile rabbit model of thoracic insufficiency syndrome (TIS) and benefits to thoracic development and respiratory function quantified. Rabbits treated early versus late were compared to age-matched normal and disease control rabbits through to skeletal maturity. OBJECTIVE: Evaluate (1) how ET changes the natural TIS disease trajectory and (2) how timing of ET affects changes in spine growth, lung growth, and respiratory mechanics. SUMMARY OF BACKGROUND DATA: Pulmonary growth potential is thought to diminish with age; thus, early therapeutic intervention may increase pulmonary growth in children with TIS. However, no direct empirical evidence exists to support this treatment paradigm. METHODS: Convex left scoliosis and resultant TIS was induced in 3-week-old rabbits via surgical rib tethering. We compare the efficacy of ET performed at 7 weeks and expanded at 11 weeks (early, n = 7) versus only at 11 weeks of age (late, n = 7) in preserving lung growth and respiratory function relative to normal (n = 8) and disease (n = 10) rabbits. Sequential computed tomography images and pulmonary function testing was performed to quantify spine curvature, lung growth, and respiratory volumes. At 28 weeks of age chest wall elastance was measured in vivo then acinar complexity analyzed histologically via radial alveolar counts. RESULTS: ET performed early or late altered the predicted trajectory of spine deformity, pulmonary growth inhibition, and respiratory dysfunction seen in disease rabbits. Growth was not significantly different between early and late rabbits and post-treatment gains remained below those of age-matched normal rabbits. Chest wall elastance was impaired by ET and more so in early rabbits, there were no differences in pulmonary elastance. CONCLUSION: ET interrupted the natural progression of deformity and pulmonary hypoplasia associated with spine curvature in disease rabbits. However, growth benefits are only seen in cases of the most severe initial deformity and must be balanced against the further impairment to chest wall function associated with repetitive surgery. LEVEL OF EVIDENCE: N/A.

Adjuvant chemotherapy for elderly patients with non-small-cell lung cancer.

Background Adjuvant chemotherapy after complete surgical resection is currently the standard of care for patients with stage IB, II, or IIIA non-small-cell lung cancer. However, the generalizability of this treatment to elderly patients is controversial. We investigated the effects of adjuvant chemotherapy in patients aged over 75 years with stage IB-IIIA non-small-cell lung cancer. Methods We retrospectively analyzed 246 consecutive patients aged over 75 years with stage IB-IIIA non-small-cell lung cancer who underwent standard lung cancer surgery between January 2001 and December 2015. They were divided into 102 who had adjuvant chemotherapy and 144 who had none (control group). The outcomes were compared between the two groups, and prognostic factors were evaluated. Results Relapse-free survival and overall survival were significantly shorter in the control group than the chemotherapy group ( p = 0.006 and p = 0.008, respectively). In multivariable analyses, adjuvant chemotherapy was found to be an independent prognostic factor for relapse-free survival and overall survival (hazard ratio = 0.594, 95% confidence interval: 0.396-0.893, p = 0.012; and hazard ratio = 0.616, 95% confidence interval: 0.397-0.957, p = 0.031, respectively). After inverse-probability-of-treatment weighting adjustment using the propensity score for baseline characteristics, chemotherapy almost improved relapse-free survival and overall survival (hazard ratio = 0.652, 95% confidence interval: 0.433-0.981, p = 0.040; and hazard ratio = 0.657, 95% confidence interval: 0.429-1.004, p = 0.052, respectively). Conclusions Adjuvant chemotherapy improved the prognosis after standard lung cancer surgery in patients aged over 75 years with stage IB-IIIA non-small-cell lung cancer.

Surgical and survival outcomes of lung cancer patients with intratumoral lung abscesses.

BACKGROUND: Intratumoral lung abscess is a secondary lung abscess that is considered to be fatal. Therefore, surgical procedures, although high-risk, have sometimes been performed for intratumoral lung abscesses. However, no studies have examined the surgical outcomes of non-small cell lung cancer patients with intratumoral lung abscesses. The aim of this study was to investigate the surgical and survival outcomes of non-small cell lung cancer patients with intratumoral lung abscesses. METHODS: Eleven consecutive non-small cell lung cancer patients with intratumoral lung abscesses, who had undergone pulmonary resection at our institution between January 2007 and December 2015, were retrospectively analysed. The post-operative prognoses were investigated and prognostic factors were evaluated. RESULTS: Ten of 11 patients were male and one patient was female. The median age was 64 (range, 52-80) years. Histopathologically, 4 patients had Stage IIA, 2 patients had Stage IIB, 2 patients had Stage IIIA, and 3 patients had Stage IV tumors. The median operative time was 346 min and the median amount of bleeding was 1327 mL. The post-operative morbidity and mortality rates were 63.6% and 0.0%, respectively. Recurrence of respiratory infections, including lung abscesses, was not observed in all patients. The median post-operative observation period was 16.1 (range, 1.3-114.5) months. The 5-year overall survival rate was 43.3%. No pre-operative, intra-operative, or post-operative prognostic factors were identified in the univariate analyses. CONCLUSION: Surgical procedures for advanced-stage non-small cell lung cancer patients with intratumoral lung abscesses, although high-risk, led to satisfactory post-operative mortality rates and acceptable prognoses.

Multilineage transduction of resident lung cells in vivo by AAV2/8 for α1-antitrypsin gene therapy.

In vivo gene delivery has long represented an appealing potential treatment approach for monogenic diseases such as α1-antitrypsin deficiency (AATD) but has proven challenging to achieve in practice. Alternate pseudotyping of recombinant adeno-associated virus (AAV) vectors is producing vectors with increasingly heterogeneous tropic specificity, giving researchers the ability to target numerous end-organs affected by disease. Herein, we describe sustained pulmonary transgene expression for at least 52 weeks after a single intratracheal instillation of AAV2/8 and characterize the multiple cell types transduced within the lung utilizing this approach. We demonstrate that lung-directed AAV2/8 is able to achieve therapeutic α-1 antitrypsin (AAT) protein levels within the lung epithelial lining fluid and that AAT gene delivery ameliorates the severity of experimental emphysema in mice. We find that AAV2/8 efficiently transduces hepatocytes in vivo after intratracheal administration, a finding that may have significance for AAV-based human gene therapy studies. These results support direct transgene delivery to the lung as a potential alternative approach to achieve the goal of developing a gene therapy for AATD.

Mechanical Forces Accelerate Collagen Digestion by Bacterial Collagenase in Lung Tissue Strips.

Most tissues in the body are under mechanical tension, and while enzymes mediate many cellular and extracellular processes, the effects of mechanical forces on enzyme reactions in the native extracellular matrix (ECM) are not fully understood. We hypothesized that physiological levels of mechanical forces are capable of modifying the activity of collagenase, a key remodeling enzyme of the ECM. To test this, lung tissue Young's modulus and a nonlinearity index characterizing the shape of the stress-strain curve were measured in the presence of bacterial collagenase under static uniaxial strain of 0, 20, 40, and 80%, as well as during cyclic mechanical loading with strain amplitudes of ±10 or ±20% superimposed on 40% static strain, and frequencies of 0.1 or 1 Hz. Confocal and electron microscopy was used to determine and quantify changes in ECM structure. Generally, mechanical loading increased the effects of enzyme activity characterized by an irreversible decline in stiffness and tissue deterioration seen on both confocal and electron microscopic images. However, a static strain of 20% provided protection against digestion compared to both higher and lower strains. The decline in stiffness during digestion positively correlated with the increase in equivalent alveolar diameters and negatively correlated with the nonlinearity index. These results suggest that the decline in stiffness results from rupture of collagen followed by load transfer and subsequent rupture of alveolar walls. This study may provide new understanding of the role of collagen degradation in general tissue remodeling and disease progression.

Extent of Spine Deformity Predicts Lung Growth and Function in Rabbit Model of Early Onset Scoliosis.

Early onset deformity of the spine and chest wall (initiated <8 years of age) is associated with increased morbidity at adulthood relative to adolescent onset deformity of comparable severity. Presumably, inhibition of thoracic growth during late stage alveolarization leads to an irreversible loss of pulmonary growth and thoracic function; however the natural history of this disease from onset to adulthood has not been well characterized. In this study we establish a rabbit model of early onset scoliosis to establish the extent that thoracic deformity affects structural and functional respiratory development. Using a surgical right unilateral rib-tethering procedure, rib fusion with early onset scoliosis was induced in 10 young New Zealand white rabbits (3 weeks old). Progression of spine deformity, functional residual capacity, total lung capacity, and lung mass was tracked through longitudinal breath-hold computed tomography imaging up to skeletal maturity (28 weeks old). Additionally at maturity forced vital capacity and regional specific volume were calculated as functional measurements and histo-morphometry performed with the radial alveolar count as a measure of acinar complexity. Data from tethered rib rabbits were compared to age matched healthy control rabbits (N = 8). Results show unilateral rib-tethering created a progressive spinal deformity ranging from 30° to 120° curvature, the severity of which was strongly associated with pulmonary growth and functional outcomes. At maturity rabbits with deformity greater than the median (55°) had decreased body weight (89%), right (59%) and left (86%) lung mass, right (74%) and left (69%) radial alveolar count, right lung volume at total lung capacity (60%), and forced vital capacity (75%). Early treatment of spinal deformity in children may prevent pulmonary complications in adulthood and these results provide a basis for the prediction of pulmonary development from thoracic structure. This model may also have future use as a platform to evaluate treatment effectiveness.

Changes in respiratory elastance after deep inspirations reflect surface film functionality in mice with acute lung injury.

Pulmonary surfactant reduces surface tension in the lung and prevents alveolar collapse. Following a deep inspiration (DI), respiratory elastance first drops then gradually increases due to surface film and tissue viscoelasticity. In acute lung injury (ALI), this increase is faster and governed by alveolar collapse due to increased surface tension. We hypothesized that the rate of increase in elastance reflects the deficiency of surfactant in the lung. To test this, mice were ventilated before (baseline) and after saline lavage obtained by injecting 0.8 ml and withdrawing 0.7 ml fluid (severe ALI) or injecting 0.1 ml (mild ALI). After two DIs, elastance was tracked for 10 min followed by a full lavage to assess surfactant proteins B (SP-B) and C (SP-C) content. Following 2 DIs, the increases in elastance during 10 min ventilation (ΔH) were 3.60 ± 0.61, 5.35 ± 1.04, and 8.33 ± 0.84 cmH2O/ml in baseline mice and mice with mild and severe ALI, respectively (P < 0.0001). SP-B and SP-C in the lavage fluid dropped by 32.4% and 24.9% in the mild and 50.4% and 39.6% in the severe ALI, respectively. Furthermore, ΔH showed a strong negative correlation with both SP-B (r(2) = 0.801) and SP-C (r(2) = 0.810) content. The ΔH was, however, much smaller when the lavage fluid also contained exogeneous SP-B and SP-C. Thus ΔH can be interpreted as an organ level measure of surface film functionality in lavage-induced ALI in mice. This method could prove useful in clinical situations such as diagnosing surfactant problems, monitoring recovery from lung injury or the effectiveness of surfactant therapy.

A Role of Myocardin Related Transcription Factor-A (MRTF-A) in Scleroderma Related Fibrosis.

In scleroderma (systemic sclerosis, SSc), persistent activation of myofibroblast leads to severe skin and organ fibrosis resistant to therapy. Increased mechanical stiffness in the involved fibrotic tissues is a hallmark clinical feature and a cause of disabling symptoms. Myocardin Related Transcription Factor-A (MRTF-A) is a transcriptional co-activator that is sequestered in the cytoplasm and translocates to the nucleus under mechanical stress or growth factor stimulation. Our objective was to determine if MRTF-A is activated in the disease microenvironment to produce more extracellular matrix in progressive SSc. Immunohistochemistry studies demonstrate that nuclear translocation of MRTF-A in scleroderma tissues occurs in keratinocytes, endothelial cells, infiltrating inflammatory cells, and dermal fibroblasts, consistent with enhanced signaling in multiple cell lineages exposed to the stiff extracellular matrix. Inhibition of MRTF-A nuclear translocation or knockdown of MRTF-A synthesis abolishes the SSc myofibroblast enhanced basal contractility and synthesis of type I collagen and inhibits the matricellular profibrotic protein, connective tissue growth factor (CCN2/CTGF). In MRTF-A null mice, basal skin and lung stiffness was abnormally reduced and associated with altered fibrillar collagen. MRTF-A has a role in SSc fibrosis acting as a central regulator linking mechanical cues to adverse remodeling of the extracellular matrix.

Noninvasive assessment for acute allograft rejection in a rat lung transplantation model.

After lung transplantation, early detection of acute allograft rejection is important not only for timely and optimal treatment, but also for the prediction of chronic rejection which is a major cause of late death. Many biological and immunological approaches have been developed to detect acute rejection; however, it is not well known whether lung mechanics correlate with disease severity, especially with pathological rejection grade. In this study, we examined the relationship between lung mechanics and rejection grade development in a rat acute rejection model using the forced oscillation technique, which provides noninvasive assessment of lung function. To this end, we assessed lung resistance and elastance (RL and EL) from implanted left lung of these animals. The perivascular/interstitial component of rejection severity grade (A-grade) was also quantified from histological images using tissue fraction (TF; tissue + cell infiltration area/total area). We found that TF, RL, and EL increased according to A-grade. There was a strong positive correlation between EL at the lowest frequency (Elow; EL at 0.5 Hz) and TF (r(2) = 0.930). Furthermore, the absolute difference between maximum value of EL (Emax) and Elow (Ehet; Emax - Elow) showed the strong relationship with standard deviation of TF (r(2) = 0.709), and A-grade (Spearman's correlation coefficients; rs = 0.964, P < 0.0001). Our results suggest that the dynamic elastance as well as its frequency dependence have the ability to predict A-grade. These indexes should prove useful for noninvasive detection and monitoring the progression of disease in acute rejection.

Proteoglycans maintain lung stability in an elastase-treated mouse model of emphysema.

Extracellular matrix remodeling and tissue rupture contribute to the progression of emphysema. Lung tissue elasticity is governed by the tensile stiffness of fibers and the compressive stiffness of proteoglycans. It is not known how proteoglycan remodeling affects tissue stability and destruction in emphysema. The objective of this study was to characterize the role of remodeled proteoglycans in alveolar stability and tissue destruction in emphysema. At 30 days after treatment with porcine pancreatic elastase, mouse lung tissue stiffness and alveolar deformation were evaluated under varying tonicity conditions that affect the stiffness of proteoglycans. Proteoglycans were stained and measured in the alveolar walls. Computational models of alveolar stability and rupture incorporating the mechanical properties of fibers and proteoglycans were developed. Although absolute tissue stiffness was only 24% of normal, changes in relative stiffness and alveolar shape distortion due to changes in tonicity were increased in emphysema (P < 0.01 and P < 0.001). Glycosaminoglycan amount per unit alveolar wall length, which is responsible for proteoglycan stiffness, was higher in emphysema (P < 0.001). Versican expression increased in the tissue, but decorin decreased. Our network model predicted that the rate of tissue deterioration locally governed by mechanical forces was reduced when proteoglycan stiffness was increased. Consequently, this general network model explains why increasing proteoglycan deposition protects the alveolar walls from rupture in emphysema. Our results suggest that the loss of proteoglycans observed in human emphysema contributes to disease progression, whereas treatments that promote proteoglycan deposition in the extracellular matrix should slow the progression of emphysema.

Emphysema and mechanical stress-induced lung remodeling.

Transpulmonary pressure and the mechanical stresses of breathing modulate many essential cell functions in the lung via mechanotransduction. We review how mechanical factors could influence the pathogenesis of emphysema. Although the progression of emphysema has been linked to mechanical rupture, little is known about how these stresses alter lung remodeling. We present possible new directions and an integrated multiscale view that may prove useful in finding solutions for this disease.

Multi-frequency forced oscillation technique using impulse oscillations: can it give mechanical information about the lung periphery?

Forced oscillation techniques (FOTs) using sine curved oscillatory waves are used for assessing the lung periphery, but measure only overall respiratory mechanics. Therefore, mathematical models of the respiratory system serve as vehicles to obtain detailed mechanics. Although the simplest model of respiratory mechanics is a simple 3-element series (RIC) model, the constant phase (CP) model is recently used for characterizing respiratory mechanics, which has the advantage of partitioning of respiratory mechanics into airway and tissue components. Meanwhile, FOTs using non-sine curved oscillatory waves are easily applied in patients with severe respiratory diseases because they do not require voluntary apnea. If the latter type of FOTs is as informative as the former, the question arises whether a FOT using non-sine curved oscillatory waves (IOS) could be used to study mechanical properties of the lung periphery. And the CP model should fit the impedance spectra. To answer this, subjects with lymphangioleiomyomatosis (LAM) were recruited as a cohort of patients with lung parenchymal disease. Impedance spectra obtained by the IOS were fitted to the CP and RIC models. Mean values of goodness of fit from the CP and RIC models were 0.978 ± 0.022 and 0.968 ± 0.026, respectively. The extra sum-of-squares F test was used to compare the two mathematical models. The F ratio was 2.37 ± 1.40 and the p-value was 0.29 ± 0.21. Unfortunately, there was no compelling evidence for adopting the CP model for the evaluation of impedance spectra obtained by IOS. This result might relate to the uncertainty of IOS for detecting mechanical properties of the lung periphery.

Improved methods for the fatty acid analysis of blood lipid classes.

Two improved methods have been developed for preparation of fatty acid methyl esters (FAME) from major O-ester lipid classes in blood, i.e., cholesterol ester, triacylglycerol, and glycerophospholipids. The methods involve simple operations, and use neither harmful solvents such as chloroform or benzene nor highly reactive volatile reagents such as acetyl chloride. The FAME synthesis reaction proceeds under mild temperature conditions. The methods include (1) extraction of lipids from 0.2 ml of blood with 0.2 ml of tert-butyl methyl ether and 0.1 ml of methanol, (2) separation of the total lipids into lipid classes using a solid-phase extraction column or thin-layer chromatography, and (3) methanolysis of each lipid class at room temperature or at 45 °C. In all the operations, solvent concentration is performed only once prior to gas-liquid chromatography (GC). No noticeable differences in composition determined by GC have been found between FAME prepared by the present methods and those prepared by a conventional method involving lipid extraction with chloroform/methanol. The mild reaction and simplified procedures of the present methods enabled safe and reproducible analysis of the fatty acid compositions of the major ester-lipid classes in blood.