Endobronchial Ultrasound Plus Fluoroscopy Versus Fluoroscopy-Guided Bronchoscopy: A Comparison of Diagnostic Yields in Peripheral Pulmonary Lesions

Background  

Even though fluoroscopy-guided bronchoscopy has been well developed, the diagnostic yield of peripheral pulmonary lesions (PPLs) remains unsatisfying. Therefore, endobronchial ultrasound (EBUS) has been implemented recently to enhance the possibility of attaining true diagnosis. However, there are few studies that directly compare the success rate of fiber-optic bronchoscopy with fluoroscopic guidance to that of EBUS guidance in the diagnosis of PPLs in the same institute and in the same study period. The aim of this study was to compare the performance of EBUS plus fluoroscopy guidance with that of fluoroscopy-guided bronchoscopy in the diagnosis of PPLs.     

The Effect of Aspiration Pressure Over Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration on the Diagnosis of Intrathoracic Lymphadenopathies

Background

Data regarding the effect of aspiration pressure over endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) on the diagnosis of intrathoracic lymphadenopathies is limited. The aim of this study was to compare the effect of three levels of aspiration pressure over EBUS-TBNA on the diagnostic yield and numbers of diagnostic cells.

Methods

A prospective study was conducted on 66 patients with enlarged intrathoracic lymph nodes. Three levels of aspiration pressure (0, 20, and 40 mL) were applied after the needle pierced the target and the needle’s position was confirmed by EBUS images. The diagnostic yield and the numbers of diagnostic cells attained with each pressure from the same target were compared. The cellularity of the obtained diagnostic cells was classified into four grades (inadequate, minimal, moderate, and numerous) by a cytopathologist in a blinded study.

Results

The mean nodal size was 19.1 ± 6.2 mm. The final diagnoses included 53 malignant and 13 benign lymphadenopathies. Adequate lymph node samples were obtained in 63 patients (95.5 %), and EBUS-TBNA revealed definite diagnosis for 58 patients (87.9 %). Negative pressure of 40 mL provided a diagnostic yield similar to that of 20 mL (83.3 vs. 75.8 %; p = 0.23), but both showed higher diagnostic yields than zero pressure. In terms of cellularity of the specimen, however, high negative pressure (40 mL) gave higher numbers of adequate cells than the comparators (p < 0.001).

Conclusion

Negative pressure should be applied in an EBUS-TBNA procedure. Although the diagnostic yield was not different, high negative pressure was superior to low negative pressure in obtaining numbers of adequate cells.     

In vitro antimalarial activity of azithromycin, artesunate, and quinine in combination and correlation with clinical outcome

Azithromycin when used in combination with faster-acting antimalarials has proven efficacious in treating Plasmodium falciparum malaria in phase 2 clinical trials. The aim of this study was to establish optimal combination ratios for azithromycin in combination with either dihydroartemisinin or quinine, to determine the clinical correlates of in vitro drug sensitivity for these compounds, and to assess the cross-sensitivity patterns. Seventy-three fresh P. falciparum isolates originating from patients from the western border regions of Thailand were successfully tested for their drug susceptibility in a histidine-rich protein 2 (HRP2) assay. With overall mean fractional inhibitory concentrations of 0.84 (95% confidence interval [CI]=0.77 to 1.08) and 0.78 (95% CI=0.72 to 0.98), the interactions between azithromycin and dihydroartemisinin, as well as quinine, were classified as additive, with a tendency toward synergism. The strongest tendency toward synergy was seen with a combination ratio of 1:547 for the combination with dihydroartemisinin and 1:44 with quinine. The geometric mean 50% inhibitory concentration (IC50) of azithromycin was 2,570.3 (95% CI=2,175.58 to 3,036.58) ng/ml. The IC50s for mefloquine, quinine, and chloroquine were 11.42, 64.4, and 54.4 ng/ml, respectively, suggesting a relatively high level of background resistance in this patient population. Distinct correlations (R=0.53; P=0.001) between quinine in vitro results and parasite clearance may indicate a compromised sensitivity to this drug. The correlation with dihydroartemisinin data was weaker (R=0.34; P=0.038), and no such correlation was observed for azithromycin. Our in vitro data confirm that azithromycin in combination with artemisinin derivatives or quinine exerts additive to synergistic interactions, shows no cross-sensitivity with traditional antimalarials, and has substantial antimalarial activity on its own.     

Randomized,Double-Blind,Placebo-Controlled Clinical Trial of a Two-Day Regimen of Dihydroartemisinin-Piperaquine for Malaria Prevention Halted for Concern over Prolonged Corrected QT Interval

Dihydroartemisinin-piperaquine, the current first-line drug for uncomplicated malaria caused by Plasmodium falciparum and Plasmodium vivax in Cambodia, was previously shown to be of benefit as malaria chemoprophylaxis when administered as a monthly 3-day regimen. We sought to evaluate the protective efficacy of a compressed monthly 2-day treatment course in the Royal Cambodian Armed Forces. The safety and efficacy of a monthly 2-day dosing regimen of dihydroartemisinin-piperaquine were evaluated in a two-arm, randomized, double-blind, placebo-controlled cohort study with 2:1 treatment allocation. Healthy military volunteers in areas along the Thai-Cambodian border where there is a high risk of malaria were administered two consecutive daily doses of 180 mg dihydroartemisinin and 1,440 mg piperaquine within 30 min to 3 h of a meal once per month for a planned 4-month period with periodic electrocardiographic and pharmacokinetic assessment. The study was halted after only 6 weeks (69 of 231 projected volunteers enrolled) when four volunteers met a prespecified cardiac safety endpoint of QTcF (Fridericia''s formula for correct QT interval) prolongation of >500 ms. The pharmacodynamic effect on the surface electrocardiogram (ECG) peaked approximately 4 h after piperaquine dosing and lasted 4 to 8 h. Unblinded review by the data safety monitoring board revealed mean QTcF prolongation of 46 ms over placebo at the maximum concentration of drug in serum (C_max) on day 2. Given that dihydroartemisinin-piperaquine is one of the few remaining effective antimalarial agents in Cambodia, compressed 2-day treatment courses of dihydroartemisinin-piperaquine are best avoided until the clinical significance of these findings are more thoroughly evaluated. Because ECG monitoring is often unavailable in areas where malaria is endemic, repolarization risk could be mitigated by using conventional 3-day regimens, fasting, and avoidance of repeated dosing or coadministration with other QT-prolonging medications. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01624337","term_id":"NCT01624337"}}NCT01624337.)     

Ex Vivo Drug Susceptibility Testing and Molecular Profiling of Clinical Plasmodium falciparum Isolates from Cambodia from 2008 to 2013 Suggest Emerging Piperaquine Resistance

Cambodia''s first-line artemisinin combination therapy, dihydroartemisinin-piperaquine (DHA-PPQ), is no longer sufficiently curative against multidrug-resistant Plasmodium falciparum malaria at some Thai-Cambodian border regions. We report recent (2008 to 2013) drug resistance trends in 753 isolates from northern, western, and southern Cambodia by surveying for ex vivo drug susceptibility and molecular drug resistance markers to guide the selection of an effective alternative to DHA-PPQ. Over the last 3 study years, PPQ susceptibility declined dramatically (geomean 50% inhibitory concentration [IC₅₀] increased from 12.8 to 29.6 nM), while mefloquine (MQ) sensitivity doubled (67.1 to 26 nM) in northern Cambodia. These changes in drug susceptibility were significantly associated with a decreased prevalence of P. falciparum multidrug resistance 1 gene (Pfmdr1) multiple copy isolates and coincided with the timing of replacing artesunate-mefloquine (AS-MQ) with DHA-PPQ as the first-line therapy. Widespread chloroquine resistance was suggested by all isolates being of the P. falciparum chloroquine resistance transporter gene CVIET haplotype. Nearly all isolates collected from the most recent years had P. falciparum kelch13 mutations, indicative of artemisinin resistance. Ex vivo bioassay measurements of antimalarial activity in plasma indicated 20% of patients recently took antimalarials, and their plasma had activity (median of 49.8 nM DHA equivalents) suggestive of substantial in vivo drug pressure. Overall, our findings suggest DHA-PPQ failures are associated with emerging PPQ resistance in a background of artemisinin resistance. The observed connection between drug policy changes and significant reduction in PPQ susceptibility with mitigation of MQ resistance supports reintroduction of AS-MQ, in conjunction with monitoring of the P. falciparum mdr1 copy number, as a stop-gap measure in areas of DHA-PPQ failure.     

Homemade talc spray atomizer dedicated to flexible-rigid pleuroscope

Background: Thoracoscopic talc poudrage is the preferred technique for medical pleurodesis. However, commercial talc spray atomizers are not applicable with the flexible‐rigid pleuroscope. Therefore, we developed a simple and cheap homemade talc spray atomizer dedicated to flexible‐rigid pleuroscope. Objective: To describe the experience in performing talc poudrage using our homemade talc spray atomizer. Methods: A retrospective review was performed in 22 consecutive patients with symptomatic malignant pleural effusion undergoing thoracoscopic talc poudrage by our talc spray atomizer with the aim of performing a palliative pleurodesis. Results: Under direct flexible‐rigid pleuroscopic guidance, we could instill talc throughout the pleural cavity with our talc spray atomizer in all cases. The median procedure time to instill the whole talc was 4 min 15 s. The successful pleurodesis was achieved in 77.3%. Conclusions: We have introduced a homemade talc spray atomizer dedicated to the flexible‐rigid pleuroscope. Uniform distribution of talc could be achieved without additional port placement. Please cite this paper as: Boonsarngsuk V, Juthakarn S and Boonsarngsuk W. Homemade talc spray atomizer dedicated to flexible‐rigid pleuroscope. Clin Respir J 2012; 6: 40–45.     

Causes of fever in adults on the Thai-Myanmar border

A hospital-based study was conducted along the Thai-Myanmar border to provide greater knowledge of the causes of febrile illness and to determine what zoonotic and vector-borne emerging infectious diseases might be present. A total of 613 adults were enrolled from June 1999 to March 2002. Cases were classified based on clinical findings and laboratory results. An etiologic diagnosis was made for 48% of subjects. Malaria was the most common diagnosis, accounting for 25% of subjects, with two-thirds Plasmodium falciparum. Serologic evidence for leptospirosis was found in 17% of subjects. Other etiologic diagnoses included rickettsial infections, dengue fever, and typhoid. The most frequent clinical diagnoses were nonspecific febrile illness, respiratory infections, and gastroenteritis. Clinical associations were generally not predictive of etiologic diagnosis. Apparent dual diagnoses were common, particularly for malaria and leptospirosis. Findings have been used to modify treatment of unspecified febrile illness in the area.