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Exhaled breath analysis for lung cancer detection using ion mobility spectrometry.

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Exhaled breath analysis for lung cancer detection using ion mobility spectrometry.

PLoS One. 2014;9(12):e114555

Authors: Handa H, Usuba A, Maddula S, Baumbach JI, Mineshita M, Miyazawa T

Abstract
BACKGROUND: Conventional methods for lung cancer detection including computed tomography (CT) and bronchoscopy are expensive and invasive. Thus, there is still a need for an optimal lung cancer detection technique.
METHODS: The exhaled breath of 50 patients with lung cancer histologically proven by bronchoscopic biopsy samples (32 adenocarcinomas, 10 squamous cell carcinomas, 8 small cell carcinomas), were analyzed using ion mobility spectrometry (IMS) and compared with 39 healthy volunteers. As a secondary assessment, we compared adenocarcinoma patients with and without epidermal growth factor receptor (EGFR) mutation.
RESULTS: A decision tree algorithm could separate patients with lung cancer including adenocarcinoma, squamous cell carcinoma and small cell carcinoma. One hundred-fifteen separated volatile organic compound (VOC) peaks were analyzed. Peak-2 noted as n-Dodecane using the IMS database was able to separate values with a sensitivity of 70.0% and a specificity of 89.7%. Incorporating a decision tree algorithm starting with n-Dodecane, a sensitivity of 76% and specificity of 100% was achieved. Comparing VOC peaks between adenocarcinoma and healthy subjects, n-Dodecane was able to separate values with a sensitivity of 81.3% and a specificity of 89.7%. Fourteen patients positive for EGFR mutation displayed a significantly higher n-Dodecane than for the 14 patients negative for EGFR (p<0.01), with a sensitivity of 85.7% and a specificity of 78.6%.
CONCLUSION: In this prospective study, VOC peak patterns using a decision tree algorithm were useful in the detection of lung cancer. Moreover, n-Dodecane analysis from adenocarcinoma patients might be useful to discriminate the EGFR mutation.

PMID: 25490772 [PubMed - in process]

Hydroxychloroquine in children with interstitial (diffuse parenchymal) lung diseases.

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Hydroxychloroquine (HCQ) is one of the drugs frequently used for the treatment of interstitial lung disease (ILD) in children (chILD). This use is off-label and studies to analyze the effect and safety of HCQ in chILD are lacking. Therefore, a literature research on the usage of chloroquine (CQ) and HCQ in these conditions was done.

Eighty-five case reports and small series in the period from 1984 to 2013 were identified in which children with different diagnoses of ILD were treated with CQ or HCQ, sometimes in combination with other medication including steroids.

A favorable response to HCQ or CQ was reported in 35 cases, whereas in the other cases the effect was negative or not clear. The dose of HCQ used was between 5 and 10 mg/kg body weight/day (bw/d). No pharmacokinetic studies have been done. The side effect profile in children seemed to be similar to that in adults. Most often gastrointestinal symptoms were reported. Three patients were found developing retinal changes during the treatment with CQ, whereas in none of the patients treated with HCQ retinal changes were reported. Based on retrospective case reports and small series likely to be reported with bias, the use of HCQ in chILD might be classified as safe. As no prospective data on efficacy and safety of HCQ in chILD are available, systematic collection is necessary.

This may be achieved by web-based registers like the European Management Platform for Childhood Interstitial Lung Diseases. Prospective and controlled investigations of HCQ in patients with chILD are mandatory. Pediatr Pulmonol. © 2014 Wiley Periodicals, Inc.

Therapeutic strategy for postoperative recurrence in patients with non-small cell lung cancer.

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Postoperative recurrence occurs in approximately half of patients with non-small cell lung cancer (NSCLC), even after complete resection. Disease recurrence after surgical resection reduces the patient's life expectancy sharply.

The prognosis after postoperative recurrence is considered to largely depend on both the mode of first recurrence (distant, locoregional or combined) and the treatment modality: (1) The majority of cases of postoperative recurrence involve distant metastasis with or without locoregional recurrence. Platinum-based systemic chemotherapy is practically accepted as the treatment for these diseases on the basis of evidence for original stage IV disease. The advent of both pemetrexed and molecular-targeted drugs has improved the survival of nonsquamous NSCLC and changed the chemotherapeutic algorithm for NSCLC; (2) Among patients with distant metastatic recurrence without locoregional recurrence at the primary tumor site, the metastasis is often limited in both organ and number. Such metastases are referred to as oligometastases. Local therapy, such as surgical resection and radiotherapy, has been suggested to be the first-line treatment of choice for oligometastatic recurrence; and (3) While locoregional recurrence is likely to cause troublesome symptoms, it is a potentially limited disease.

Therefore, providing local control is important, and radiation is usually beneficial for treating local recurrence. In order to obtain better control of the disease and provide treatment with curative intent in patients with limited disease, the administration of concurrent platinum-based chemoradiotherapy is recommended according to the results of originally nonresectable stage IIIA and IIIB disease.

Performance Comparisons of Jet and Mesh Nebulizers Using Different Interfaces in Simulated Spontaneously Breathing Adults and Children.

Different types of nebulizers and interfaces are used for the treatment of adults and children with pulmonary diseases. The purpose of this study was to determine the efficiency of a mesh nebulizer (MN) with a proprietary adapter and a jet nebulizer (JN) under different configurations in adult and pediatric models of spontaneous breathing.

We hypothesize that delivery efficiency of JN and MN will differ depending on the interface used during aerosol therapy in simulated spontaneously breathing adult and pediatric models. While we expect that aerosol delivery with JN will be less efficient than MN, we also hypothesize that lung deposition obtained with the adult lung model will be more than that with the pediatric lung model in all conditions tested in this study.

Methods: A lung model using a teaching manikin connected to a sinusoidal pump via a collecting filter at the level of the bronchi simulating a spontaneously breathing adult (Vt 500 mL, RR 15 bpm, I:E ratio 1:2) or pediatric patient (Vt 150 mL, RR 25 bpm, I:E ratio 1:2). Albuterol sulfate (2.5 mg/3 mL) was aerosolized with JN (Mistymax 10, Airlife) or MN (Aerogen Solo(®), Aerogen) with the Adapter (Aerogen Solo(®) Adapter, Aerogen Ltd, Galway, Ireland) using mouthpiece, aerosol mask, and valved-mask in adults and the dragon mask, aerosol mask, and valved-mask in pediatrics (n=3). The Adapter, specifically designed for MN, was attached to all the interfaces used in this study with supplemental oxygen of 2 lpm, and in addition, the MP was tested with no additional flow in the adult model. The JN was driven with 10 lpm based on the manufacturer's label. Drug was eluted from the filter and analyzed via spectrophotometry. Descriptive statistics, dependent t-test and one-way analysis of variance were used for data analysis. Significant level was set at 0.05.

Results: In adults, delivery efficiency of JN with the valved mask was significantly greater than that with the aerosol mask (p=0.01). Aerosol delivery of JN with the mouthpiece was not statistically significant from the valved mask (p=0.123) and the aerosol mask (p=0.193). Drug delivery with MN with mouthpiece (15.42±1.4%) and valved-mask (15.15±1.1%) was greater than the open aerosol mask (7.54±0.39%; p=0.0001) in the adult lung model. With no flow mouthpiece delivery increased>2 fold (34.9±3.1%; p=.0001) compared to use of 2 lpm of flow. Using the JN with the pediatric model deposition with valved-mask (5.3±0.8%), dragon mask (4.7±0.9%), and aerosol mask (4.1±0.3%) were similar (p>0.05); while drug delivery with MN via valved-mask (11.1±0.7%) was greater than the dragon mask (6.44±0.3%; p=0.002) and aerosol mask (4.6±0.4%; p=0.002), and the dragon mask was more efficient than the open aerosol mask (p=0.009)

Conclusion: The type of nebulizer and interface used for aerosol therapy affects delivery efficiency in these simulated spontaneously breathing adult and pediatric models. Drug delivery was greatest with the valved-mouthpiece and mask with JN and MN, while the standard aerosol mask was least efficient in these simulated spontaneously breathing adult and pediatric lung models. Delivery efficiency of JN was less than MN in all conditions tested in this study except in the aerosol mask. Lung deposition obtained with the adult lung model was more than that with the pediatric lung model.

Segmental Approach to Lung Volume Reduction Therapy for Emphysema Patients

Emphysema is often distributed heterogeneously throughout the lungs, even at the segmental level. It is important for interventional lung volume reduction therapies to target and treat the most diseased regions of the lung while preserving the less diseased functional regions. Identification and determination of the severity of emphysema can be done using the various quantification measures reviewed in this article. However, all of these measures are similar in what they quantify and are equally good indicators of emphysema. The tissue/air ratio was chosen for our purposes. Software capable of quantifying emphysema severity at the segmental level exists, and can be utilized to identify the most diseased segments while following anatomical boundaries. The segmental heterogeneity index is a ...

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