Alexander Guber

Maximum expiratory flow-volume curve: mathematical model and experimental results

A mathematical simulation of the maximum expiratory flow-volume (MEFV) curve was developed using a lumped parameter model. The model uses a theoretical approximation of an activation function representing the lungs pressure-volume relationship during maximally forced expiration. The waveforms obtained by the model were compared to the flow-volume curves recorded from normal subjects and for patients with small airways disease, asthma, and emphysema. We were able to reproduce the flow-volume curves using the model and calculate new parameters that reflect the dependency of airways resistance on expired volume during FVS manoeuvre. These new parameters are based on the entire information presented in the flow-volume curve and on the reduction in flow at all lung volumes. We also calculated the mean slope of the resistance-expired volume curves obtained from the model by fitting a straight line to the curve. Using representative data for normal and COPD patients different mean slopes of 0.095, 0.13, 0.49 and 1.44 litre-1 were obtained for normal subject, small airways disease, asthma and emphysema patients, respectively. The model-based parameters may be applicable to human studies. However, further studies in large groups of patients are required to better define the true predictive value of the new indices described for the diagnosis of COPD.

Computerized analysis of cytology and fluorescence in situ hybridization (FISH) in induced sputum for lung cancer detection

Lung cancer results from a multistep process, whereby genetic and epigenetic alterations lead to a malignant phenotype. Somatic mutations, deletions, and amplifications can be detected in the tumor itself, but they can also be found in histologically normal bronchial epithelium as a result of field cancerization. The present feasibility study describes a computer‐assisted analysis of induced sputum employing morphology and fluorescence in situ hybridization (target–FISH), using 2 biomarkers located at chromosomes 3p22.1 and 10q22.3.

Immunocytochemical characterization of lung tumors in fine‐needle aspiration. The use of cytokeratin monoclonal antibodies for the differential diagnosis of squamous cell carcinoma and adenocarcinoma

In the current study, immunocytochemical typing of intermediate filaments was used for a differential diagnosis of human lung tumors from transthoracic fine‐needle aspiration biopsies (TFNAB). The authors have compared the cytologic diagnosis of 53 lung cancer cases with the immunofluorescence patterns obtained using a panel of monoclonal antibodies, five of which (KG 8.13, KM 4.62, Ks B.17, KS 8.12, KK 8.60) react with specific cytokeratin polypeptides and one with vimentin (VIM 13.2). Only in six of 23 samples cytologically diagnosed as squamous cell carcinoma did the immunocytochemical typing of cytokeratins (ICTC) confirm the cytologic diagnosis. In seven cases some of the tumor cells stained positively with antibody Ks B.17 specific for simple epithelial keratin (No: 18), suggesting the presence of some cells of glandular origin. In ten additional cases the ICTC was in conflict with the cytologic diagnosis of squamous cell carcinoma (i.e., antibodies Ks 8.12 and KK 8.60 were negative, and antibody Ks B.17, positive) supporting a diagnosis of adenocarcinoma. In 14 of 18 cases cytologically diagnosed as adenocarcinoma, the ICTC confirmed the diagnosis whereas in four cases additional presence of some squamous cells was noticed. The ICTC labeling of cases cytologically diagnosed as undifferentiated and large cell carcinomas was similar to that of the group of adenocarcinomas. Thus, the application of cytokeratin typing for TFNAB samples seems to provide a vital complementation to routine cytologic study, especially for cases cytologically diagnosed as squamous carcinoma.

Increased hypoxemia in patients with COPD and pulmonary hypertension undergoing bronchoscopy with biopsy

Background and objective Patients with pulmonary hypertension (PH) are considered to be at risk for complications associated with flexible bronchoscopy (FB), but data concerning the degree of PH are often lacking. We investigated whether COPD patients with PH who undergo bronchoscopy are at greater risk for complications. Methods This prospective study included 207 consecutive COPD patients undergoing FB. All underwent an echo-Doppler to evaluate pulmonary artery pressure on the day of the bronchoscopy procedure. Pulmonologists were blinded to the echocardiogram results. Results A total of 167 patients (80.7%) had normal pulmonary pressure. The remaining 40 patients (19.3%) had PH: 27 (13.0%) mild, eight (3.9%) moderate, and five (2.4%) severe. Noninvasive hemodynamic parameters between groups before and after FB were similar. Two patients with normal pulmonary pressure developed supraventricular tachycardia. None developed hemodynamically significant dysrhythmia. Bleeding episodes between groups in bronchoalveolar lavage (BAL) and transbronchial biopsy (TBB) did not differ. PH patients who underwent BAL and TBB had decreased O2 saturation during the procedure compared with the non-PH group (23.5% vs 6.9%, P=0.033). No deaths were attributable to FB. Conclusion PH is common among COPD patients undergoing FB. PH patients undergoing BAL and TBB are at higher risk of decreased O2 saturation than those without PH. Further studies should assess the risk among COPD patients with moderate-to-severe PH.

Model-based prediction of expiratory resistance index in patients with asthma

Objectives. Develop a sensitive algorithm and index for detection of asthma patients using forced expiratory flow curves. Methods. A lumped-parameter model of forced expiration was developed. The model can predict the flow-volume curve during forced expiratory maneuver. The flow-volume curves generated by the model depend on values of resistance parameters (FER). Use of flow-volume curves recorded from normal subjects and from patients with asthma before and after ventolin inhalation as inputs for the inverse model, yielded the resistance parameters for each case. These parameters are based on the entire information presented in the flow-volume curve and on the reduction in flow at all lung volumes. Results. Forced Expiratory Resistance (FERN) indices were estimated at different percent of lung volumes using the inverse model. The index was significantly affected by inhalation of ventolin in asthmatic patients and was insensitive to ventolin inhalation in normal patients. In asthmatic patients, the FER index at five lung volumes (out of eight), was two–five times greater than in normal subjects with p ≪ 0.05 (three of them with p ≪ 0.01). Conclusions. The estimated parameters were sensitive indicators of the degree of lung function impairment and were able to accurately distinguish between healthy and asthmatic patients.

The forced expiratory volume-time curve estimation using the electrocardiogram

The feasibility of estimating the forced expiratory volume-time curve from the amplitude modulation of the electrocardiogram was studied using a numerical torso model and ECG signal processing. A two dimensional numerical model of the torso was solved for the maximum expiration and inspiration to study the changes in the surface potential as a result of changes in the lung volume. The numerical model showed that significant changes in the surface potential amplitude occur between maximum inspiration and maximum expiration and that this amplitude change in the left-right axis of the torso might be three times as large as in the front-back axis. In the experimental setup, ECG waveforms from the surface of the chest and the mouth air flow were simultaneously recorded from four male subjects during several forced vital capacity (FVC) maneuvers. The amplitude of the QRS complex was measured for different expired lung volumes and an estimation of the forced expiratory volume-time curve was obtained. The FVC and the FEV1 (forced expiratory volume after 1 s) spirometry indices were calculated for the two volume-time curves obtained from the electrocardiogram and from the spirometry measurements. The results differ between 0.1 and 0.8 1. These preliminary results are encouraging and might indicate that a relationship between the volume-time curve during FVC test and the electrocardiogram signals does exist. Further validation in a larger number of subjects and patients is needed before the technique can be applicable for clinical use.

Inhaled Tranexamic Acid for Hemoptysis Treatment

BACKGROUND: Tranexamic acid (TA) is an antifibrinolytic drug currently used systemically to control bleeding. To date, there have been no prospective studies of the effectiveness of inhaled TA for the treatment of hemoptysis. OBJECTIVES: The goal of this study was to prospectively assess the effectiveness of TA inhalations (ie, nebulized TA) for hemoptysis treatment. METHODS: This analysis was a double‐blind, randomized controlled trial of treatment with nebulized TA (500 mg tid) vs placebo (normal saline) in patients admitted with hemoptysis of various etiologies. Patients with massive hemoptysis (expectorated blood > 200 mL/24 h) and hemodynamic or respiratory instability were excluded. Mortality and hemoptysis recurrence rate were assessed at 30 days and following 1 year. RESULTS: Forty‐seven patients were randomized to receive TA inhalations (n = 25) or normal saline (n = 22). TA was associated with a significantly reduced expectorated blood volume starting from day 2 of admission. Resolution of hemoptysis within 5 days of admission was observed in more TA‐treated patients than in those receiving placebo (96% vs 50%; P < .0005). Mean hospital length of stay was shorter for the TA group (5.7 ± 2.5 days vs 7.8 ± 4.6 days; P = .046), with fewer patients requiring invasive procedures such as interventional bronchoscopy or angiographic embolization to control the bleeding (0% vs 18.2%; P = .041). No side effects were noted in either group throughout the follow‐up period. In addition, a reduced recurrence rate was noted at the 1‐year follow‐up (P = .009). CONCLUSIONS: TA inhalations can be used safely and effectively to control bleeding in patients with nonmassive hemoptysis. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01496196; URL: www.clinicaltrials.gov.

The role of bacterial culture by bronchoscopy in patients with lung cancer: a prospective study

Background Patients with lung cancer undergoing surgical and medical treatment are at increased risk for pulmonary complications. The importance of routine bronchoscopy procedure in populations with lung cancer has rarely been defined. We aimed to determine the growth of potentially pathogenic microorganisms (PPM) among patients evaluated by bronchoscopy for lung cancer. Methods This prospective study included 155 consecutive patients with lung mass or radiologic findings suspicious for malignancy. Baseline demographic, clinical and radiologic features were collected. Clinical features of infection were compared to microbiologic and histologic results. Results The bacterial spectrum of lung cancer patients was similar to those without malignancy. The most frequently isolated organisms were Pseudomonas sp. and Staphylococcus aureus. Among all patients, bronchial bacterial positive PPM growth was noted in 30% (46/155). The significant PPM growth rate was three-fold higher among those with clinical signs of infection (P<0.001). Interestingly, 30 of these 46 patients (66%) did not show signs of clinical infection. Conclusions Bronchoscopic evaluations should include bacterial cultures for direct targeted antibiotic therapy only in the symptomatic patients.