Machine learning computational model to predict lung cancer using electronic medical records.

BACKGROUND: Lung cancer (LC) screening using low-dose computed tomography (CT) is recommended according to standard risk criteria or personalized risk calculators. Machine learning (ML) models that can predict disease risk are an emerging method in medicine for identifying hidden associations that are personally unique. MATERIALS AND METHODS: Using the tree-based pipeline optimization tool (TPOT), we developed an ML-based model, which is an ensemble of the Random Forest and XGboost models, based on known risk factors for LC, as part of a larger trial for ML prediction using electronic medical records and chest CT. We used data from patients with LC vs. controls (1:2) of patients aged ≥ 35 years. We developed a model for all LC patients as well as for patients with and without a smoking background. We included age, gender, body mass index (BMI), smoking history, socioeconomic status (SES), history of chronic obstructive pulmonary disease (COPD)/emphysema/chronic bronchitis (CB), interstitial lung disease (ILD)/pulmonary fibrosis (PF), and family history of LC. RESULTS: Of the 4076 patients, 1428 (35 %) were in the LC group and 2648 (65 %) were in the control group. For the entire study population, our model achieved an accuracy of 71.2 %, with a sensitivity of 69 % and a positive predictive value (PPV) of 74 %. Higher accuracy was achieved for the two subgroups. An accuracy of 74.8 % (sensitivity 72 %, PPV 76 %) and 73.0 % (sensitivity 76 %, PPV 72 %) was achieved for the smoking and never-smoking cohorts, respectively. For the entire population and smoker cohort, COPD/emphysema/CB were the most important contributors, followed by BMI and age, while in the never-smoking cohort, BMI, age and SES were the most important contributors. CONCLUSION: Known risk factors for LC could be used in ML models to modestly predict LC. Further studies are needed to confirm these results in new patients and to improve them.

Association between obstructive sleep apnea (OSA) and COVID-19 severity.

Obstructive sleep apnea and sleep-related hypoxia have been associated with higher rates of hospitalization and mortality among patients with Coronavirus disease 2019 (COVID-19). We further explored the association between obstructive sleep apnea, COVID-19 severity and related mortality. In addition, we examined the effects of clinical and demographic parameters on COVID-19. In this retrospective study, we included adult patients who were diagnosed with COVID-19 prior to the Omicron variant identification. We compared the severity of COVID-19 and mortality with the diagnosis of obstructive sleep apnea. The study population included 44,275 patients who tested positive for COVID-19. Of these, 97% had mild or asymptomatic disease, 1.2% had moderate disease, and 1.8% had severe disease. Obstructive sleep apnea was diagnosed in 980 (2.2%) patients. In a multivariate analysis, obstructive sleep apnea diagnosis increased the risk of severe COVID-19 by 1.6 (95% confidence interval: 1.1-2.4) compared with mild disease. However, no increase in mortality was associated with obstructive sleep apnea. Interestingly, patients with moderate and high socioeconomic status had a 1.6 times higher risk for severe COVID-19 than patients from the low socioeconomic status group (95% confidence interval: 1.2-2.1 and 95% confidence interval: 1.1-2.3, respectively). The risk of dying due to COVID-19 was 1.6 (95% confidence interval: 1.1-2.5) and 3.1 (95% confidence interval: 1.8-5.3) times higher in patients with medium and high socioeconomic status, respectively, compared with patients with low socioeconomic status. Diagnosis of obstructive sleep apnea was found to be an independent risk factor for severe COVID-19. The higher the socioeconomic status, the higher the risk of severe COVID-19 morbidity and mortality.

Attitudes toward COVID-19 vaccination of healthcare workers in Israel and vaccination rates during vaccine rollout.

A new COVID-19 vaccine was introduced in a remarkably short period of time. Public and healthcare workers (HCWs) were concerned about the safety of the vaccine, especially in light of the use of new technologies. A review regarding attitudes towards COVID-19 vaccination found a 22.5% hesitancy rate among HCWs. Online anonymous questionnaires were delivered using a web-based surveying platform to community HCWs in a central district in Israel from 3 to 19 January 2021. The real COVID-19 vaccination data were collected between the beginning of the vaccination rollout and the end of the month after the survey as well as the real vaccination rate among the general population. Of the 3,172 HCWs, 549 (17%) responded to the questionnaire. The highest positive attitude towards the vaccine was among physicians (95%), while nurses showed the highest level of hesitation (14%) for a specific sector (P < 0.05). However, the real vaccination rates were similar among physicians (63%) and nurses (62%). Surprisingly, the total vaccination rate of HCWs was substantially lower (52%) than that of the general population (71%). The main vaccination motivators were the social and economic effects of the COVID-19 epidemic. Focused strategies to reduce the level of hesitancy among HCWs are needed.

Postexposure-vaccine-prophylaxis against COVID-19.

During the COVID-19 pandemic, postexposure-vaccine-prophylaxis is not a practice. Following exposure, only patient isolation is imposed. Moreover, no therapeutic prevention approach is applied. We asked whether evidence exists for reduced mortality rate following postexposure-vaccine-prophylaxis. To estimate the effectiveness of postexposure-vaccine-prophylaxis, we obtained data from the Israeli Ministry of Health registry. The study population consisted of Israeli residents aged 12 years and older, identified for the first time as PCR-positive for SARS-CoV-2, between December 20th, 2020 (the beginning of the vaccination campaign) and October 7th, 2021. We compared "recently injected" patients-that proved PCR-positive on the same day or on 1 of the 5 consecutive days after first vaccination (representing an unintended postexposure-vaccine-prophylaxis)s-to unvaccinated control group. Among Israeli residents identified PCR-positive for SARS-CoV-2, 11 687 were found positive on the day they received their first vaccine injection (BNT162b2) or on 1 of the 5 days thereafter. In patients over 65 years, 143 deaths occurred among 1412 recently injected (10.13%) compared to 255 deaths among the 1412 unvaccinated (18.06%), odd ratio (OR) 0.51 (95% confidence interval [CI]: 0.41-0.64; p < 0.001). A significant reduction in the death toll was observed among the 55-64 age group, with 8 deaths occurring among the 1320 recently injected (0.61%) compared to 24 deaths among the 1320 unvaccinated control (1.82%), OR 0.33 (95% CI: 0.13-0.76; p = 0.007). Postexposure-vaccine-prophylaxis is effective against death in COVID-19 infection.

Duplicate Prescription Rates of Long-Acting Bronchodilator Inhalers.

Background: Long-acting bronchodilator inhalers are widely used with or without inhaled corticosteroids (ICs) by patients with lung diseases. In Israel alone, there are 21 inhalers containing long-acting ß2 agonists (LABAs) and/or long-acting muscarinic antagonists (LAMAs). Some patients are treated incorrectly with several inhalers of the same pharmacologic group. Methods: Electronic data of LABA and/or LAMA inhalers purchased during a period of 1 year were extracted in one district of Clalit Health Services in Israel. Patients who were treated with two or more inhalers from the same pharmacologic group were compared with patients without duplicate treatment. Inhaler purchases during the 12 months before and after the first duplicate purchase were compared with the purchases by patients without duplication of treatment. New diagnoses were compared to identify possible side effects. Results: Of the 13,528 patients who were treated with LABA and/or LAMA inhalers, 244 (1.8%) purchased at least two different inhalers from the same pharmacologic group. Inhaler purchases were 3.8 times higher in the duplication group during the 12 months before the first duplication. Inhaler purchase increased by 28% in the duplication group compared with a 4.5% increase in the nonduplication group (p < 0.001) during the following year. The risk for duplicated consumption was significantly higher in patients with a chronic obstructive pulmonary disease (COPD) diagnosis, males, and persons aged between 61 and 80 years. Conclusions: Nearly 2% of the patients treated with long-acting bronchodilators consumed different medications of the same pharmacologic group even when adherence was satisfactory. COPD patients are at higher risk for inhaler duplication. Clinical Trial Registration Number: 0151-20-COM1.

Short-acting bronchodilators purchase as a marker for asthma control.

Background: Administrative data has been used to quantify the amount of medication use in order to identify at-risk asthma patients. In our previous study we used short-acting beta-agonists (SABA) inhalers as a marker for asthma control.Methods: We further analyzed patient data from the SABA inhalers study in which asthma control was classified by GINA guidelines, physician assessment and the patients overall estimation. We identified all short-acting bronchodilator purchases (SABA and anticholinergic inhalers and solutions) in the year prior to administering the questionnaire relating to asthma control, and compared inhaled and systemic steroid use.Results: Of 241 asthma patients, 83 completed questionnaires. Using the GINA guidelines criteria, 26 were symptom controlled, 46 were partially controlled and 11 were uncontrolled. Using patients' overall impression of their asthma control, mean annual short-acting bronchodilator purchases were significantly higher in the partially controlled and uncontrolled patients (10 and 8.9 respectively) than in the controlled patients (2, p = 0.005). Most asthma patients purchase less than half of the controller medications prescribed to them.Conclusion: When using administrative data, 3 or more -of all types of short-acting bronchodilator purchases in one year should alert the physician to evaluate asthma control and purchase alerts should notify both physicians and patients when controller consumption is low.

Increased Risk for Cancer in Young Patients with Severe Obstructive Sleep Apnea.

BACKGROUND: Several studies in animal models and human with obstructive sleep apnea syndrome (OSAS) demonstrated an increase in cancer aggressiveness and mortality. However, there is a need for further clinical evidence supporting a correlation between OSAS and cancer incidence. OBJECTIVES: To reveal whether OSAS presence and severity is correlated with cancer incidence in a large homogenous patients' cohort. METHODS: We analyzed a cohort of over 5,000 concurrently enrolled patients, age > 18, with suspected OSAS, from a tertiary medical academic center. Patients underwent whole night polysomnography, the gold standard diagnostic tool for OSAS, and were classified for severity according to the Apnea Hypopnea Index (AHI). Data on cancer incidence were obtained from the Israel National Cancer Registry. A multivariate Cox proportional-hazards analysis, adjusted for age, gender, and BMI, was performed to estimate the hazard-ratio of new cancer incidence. RESULTS: Among 5,243 subjects with a median follow-up of 5.9 years, 265 were diagnosed with cancer. The most prevalent cancers were prostate (14.7%), hematological (12.8%), urothelial (9.4%), colorectal (9%), and breast (8.3%). In subjects who were diagnosed at age below 45 years (n = 1,533), a high AHI (> 57/h) was significantly associated with cancer (HR 3.7, CI 1.12-12.45, p = 0.008). CONCLUSIONS: Patients younger than 45 with severe OSAS have a significantly higher all-type cancer incidence than the general population. These results should encourage clinicians to detect and diagnose young patients with suspected OSAS and to recommend cancer screening methods in this high-risk population.

Non-invasive early detection of malignant pulmonary nodules by FISH-based sputum test.

BACKGROUND: Early detection decreases lung cancer mortality. The Target-FISH Lung Cancer Detection (LCD) Test is a non-invasive test designed to detect chromosomal changes (deletion or amplification) via Fluorescence in situ Hybridization (FISH) in sputum specimens from persons suspected of having lung cancer. We evaluated the performance of the LCD test in patients with highly suspicious pulmonary nodules who were scheduled for a biopsy procedure. METHODS: Induced sputum was collected from patients who were scheduled for biopsy of a solitary pulmonary nodule (0.8-3 cm) in one of 6 tertiary medical centers in the US and Israel. The lung cancer detection (LCD) Test combined sputum cytology and Target-FISH analysis on the same target cells and the results were compared to the pathology. Participants with non-surgical negative biopsy results were followed for 2 years to determine their final diagnosis. RESULTS: Of the 173 participants who were evaluated, 112 were available for analysis. Overall, the LCD test had a sensitivity of 85.5% (95% CI, 76.1-92.3), specificity of 69% (95% CI, 49.2-84.7) and an accuracy of 81.3% (95% CI, 72.8-88). The positive and negative predictive values (PPV, NPV) were 88.8% and 62.5%, respectively. The LCD test was positive in 9 of 11 lung cancer patients who had an initial negative biopsy. CONCLUSIONS: In a cohort of patients with highly suspicious lung nodules, the LCD test is a non-invasive option with good sensitivity and a high positive predictive value. A positive LCD test reinforces the need to aggressively pursue a definitive diagnosis of suspicious nodules.

Chronic iliofemoral vein obstruction - an under-recognized cause of exercise limitation.

Local symptoms of chronic venous insufficiency after deep vein thrombosis (DVT) are well described, but little is known about the effect of residual venous obstruction on exercise capacity. We tested our hypothesis that chronic residual iliofemoral vein occlusion (IFVO) after DVT may impair exercise capacity. Nine post-DVT patients with residual IFVO and effort intolerance were studied; a comparison cohort consisted of 11 healthy volunteers. Exercise tolerance was assessed by bimodality incremental symptom-limited cardiopulmonary testing, using leg and arm ergometers. In healthy subjects, leg vein obstruction was modelled by application to the thighs of cuff tourniquets inflated to 30-40 mmHg. Leg exercise tolerance as measured by oxygen uptake at peak exercise (peak ⩒'O2) was reduced in patients (median 50% predicted (range 36-83%) vs. 88% predicted (67-129%) in normal subjects, p < 0.001). Arm exercise tolerance was also reduced in patients, but less severely than in the legs - the median arm: leg ratio of peak ⩒'O2 was 0.95 (0.77-1.43) in patients vs. a normal ratio of 0.73 (0.6-1.0) in healthy subjects (p < 0.003). In healthy subjects, bilateral leg vein obstruction by tourniquets reduced peak ⩒'O2 in leg exercise to 76% predicted (range 55-108%; p < 0.001 vs. standard test). In conclusion, the comparison of arm vs. leg exercise capacity in post-DVT patients with residual IFVO and the effect of experimental venous obstruction (thigh tourniquets) in healthy subjects suggest that reduced exercise capacity in patients was at least partially caused by reduced venous return. Chronic venous obstruction should be recognized as a cause of exercise limitation.

Determination of asthma control using administrative data regarding short-acting beta-agonist inhaler purchase.

BACKGROUND: Symptom control is a primary goal in asthma. We hypothesized that administrative data regarding rescue inhaler purchases may correlate with asthma symptom control. METHODS: We identified all patients who purchased short-acting beta-agonist (SABA) inhalers during the course of one year in the database of a Health Maintenance Organization (HMO). Primary physicians identified asthma patients and classified their asthma symptom control into three groups according to the Global Initiative for Asthma (GINA) guidelines. Asthma patients were asked to answer symptom questionnaires and grade their asthma control. SABA inhaler purchases were compared between asthma control groups as classified by the guidelines, the physicians and the patients. We also compared the agreement on asthma control between the three methods of classification. RESULTS: Of 241 asthma patients, 83 completed the questionnaires. Using the GINA guidelines criteria, 26 were symptom controlled, 46 were partially controlled and 11 were uncontrolled. SABA inhaler purchases were not significantly lower in the controlled group. Using patients' overall impression of their asthma control, the mean numbers of SABA inhalers purchased were 1.5, 4.4 and 6.4 per year in the controlled, partially controlled and uncontrolled groups, respectively (p = 0.03). Patients' classification of asthma control had better agreement (kappa = 0.34) with GINA guidelines than physician's' agreement (kappa = 0.05). CONCLUSION: When using administrative data for asthma patients, 2 or more SABA inhaler purchases in one year should alert the physician for the need for asthma control evaluation. Purchase of at least 4 SABA inhalers a year may be regarded as a marker for asthma that is not controlled.

Detection of Lung Cancer and EGFR Mutation by Electronic Nose System.

INTRODUCTION: Early detection of lung cancer (LC) has been well established as a significant key point in patient survival and prognosis. New highly sensitive nanoarray sensors for exhaled volatile organic compounds that have been developed and coupled with powerful statistical programs may be used when diseases such as LC are suspected. Detection of genetic aberration mutation by nanoarray sensors is the next target. METHODS: Breath samples were taken from patients who were evaluated for suspicious pulmonary lesions. Patients were classified as those with benign nodules, as patients with LC with or without the EGFR mutation, and according to their smoking status. Breath prints were recognized by nanomaterial-based sensor array, and pattern recognition methods were used. RESULTS: A total of 119 patients participated in this study, 30 patients with benign nodules and 89 patients with LC (16 with early disease and 73 with advanced disease). Patients with LC who harbored the EGFR mutation (n = 19) could be discriminated from those with wild-type EGFR (n = 34) with an accuracy of 83%, sensitivity of 79%, and specificity of 85%. Discrimination of early LC from benign nodules had 87% accuracy and positive and negative predictive values of 87.7 and 87.5% respectively. Moderate discrimination (accuracy of 76%) was found between LC of heavy smokers and that of never-smokers or distant past light smokers. CONCLUSIONS: Breath analysis could discriminate patients with LC who harbor the EGFR mutation from those with wild-type EGFR and those with benign pulmonary nodules from those patients with early LC. A positive breath print for the EGFR mutation may be used in treatment decisions if tissue sampling does not provide adequate material for definitive mutation analysis.

Exhaled Breath Analysis for Monitoring Response to Treatment in Advanced Lung Cancer.

INTRODUCTION: The Response Evaluation Criteria in Solid Tumors (RECIST) serve as the accepted standard to monitor treatment efficacy in lung cancer. However, the time intervals between consecutive computerized tomography scans might be too long to allow early identification of treatment failure. This study examines the use of breath sampling to monitor responses to anticancer treatments in patients with advanced lung cancer. METHODS: A total of 143 breath samples were collected from 39 patients with advanced lung cancer. The exhaled breath signature, determined by gas chromatography/mass spectrometry and a nanomaterial-based array of sensors, was correlated with the response to therapy assessed by RECIST: complete response, partial response, stable disease, or progressive disease. RESULTS: Gas chromatography/mass spectrometry analysis identified three volatile organic compounds as significantly indicating disease control (PR/stable disease), with one of them also significantly discriminating PR/stable disease from progressive disease. The nanoarray had the ability to monitor changes in tumor response across therapy, also indicating any lack of further response to therapy. When one-sensor analysis was used, 59% of the follow-up samples were identified correctly. There was 85% success in monitoring disease control (stable disease/partial response). CONCLUSION: Breath analysis, using mainly the nanoarray, may serve as a surrogate marker for the response to systemic therapy in lung cancer. As a monitoring tool, it can provide the oncologist with a quick bedside method of identifying a lack of response to an anticancer treatment. This may allow quicker recognition than does the current RECIST analysis. Early recognition of treatment failure could improve patient care.

Screening for lung cancer: time for large-scale screening by chest computed tomography.

Lung cancer is the leading cause of cancer death worldwide. Age and smoking are the primary risk factors for lung cancer. Treatment based on surgical removal in the early stages of the disease results in better survival. Screening programmes for early detection that used chest radiography and sputum cytology failed to attain reduction of lung cancer mortality. Screening by low-dose computed tomography (CT) demonstrated high rates of early-stage lung cancer detection in a high-risk population. Nevertheless, no mortality advantage was manifested in small randomised control trials. A large randomised control trial in the U.S.A., the National Lung Screening Trial (NLST), showed a significant relative reduction of 20% in lung cancer mortality and 6.7% reduction in total mortality, yet no reduction was evidenced in the late-stage prevalence. Screening for lung cancer by low-dose CT reveals a high level of false-positive lesions, which necessitates further noninvasive and invasive evaluations. Based primarily on the NLST eligible criteria, new guidelines have recently been developed by major relevant organisations. The overall recommendation coming out of this collective work calls for lung cancer screening by low-dose CT to be performed in medical centres manned by specialised multidisciplinary teams, as well as for a mandatory, pre-screening, comprehensive discussion with the patient about the risks and advantages involved in the process. Lung cancer screening is on the threshold of a new era, with ever more questions still left open to challenge future studies.

Endobronchial drainage of lung abscess: the use of laser.

The management of lung abscess is usually conservative. However, in some cases drainage is necessary, commonly performed transcutaneously. Endobronchial catheter drainage is a potential alternative, though reported only sporadically. Transbronchial pigtail catheter drainage was used in 3 patients with refractory lung abscesses at our centre. The catheter was introduced endobronchially under bronchoscopic procedure. Laser was used to perforate the abscess wall through the airway into the abscess in order to provide a pathway for catheter insertion. An improvement in clinical and radiological parameters was noted immediately after catheter placement. The catheters were extracted after 4-6 days. All patients had a complete clinical recovery. Endobronchial catheters with the use of laser appear to be relatively safe and effective for the treatment of pulmonary abscess in selected patients in whom the abscess is adjacent to the central airway. When necessary, a bulge in an adjacent airway can be perforated with laser. To the best of our knowledge, there have been no previous reports of endobronchial drainage with the use of laser.

Peripheral arterial stiffness and endothelial dysfunction in idiopathic and scleroderma associated pulmonary arterial hypertension.

OBJECTIVE: Pulmonary endothelial dysfunction and increased reflection of pulmonary pressure waves have been reported in pulmonary arterial hypertension (PAH). However, the systemic vascular involvement is not fully understood. Our study focused on the systemic arterial stiffness and endothelial involvement in idiopathic and scleroderma associated PAH. METHODS: Peripheral arterial stiffness and endothelial function were evaluated in 38 patients with idiopathic (n = 28) and scleroderma associated (n = 10) PAH, and 21 control subjects (13 healthy; 8 with scleroderma and normal pulmonary pressure). All participants underwent clinical and cardiopulmonary evaluation. Arterial stiffness was measured through the fingertip tonometry derived augmentation index (AI), which is the boost increase in the late systolic pressure wave after the initial systolic shoulder. Endothelial function was measured by forearm blood flow dilatation response to brachial artery occlusion by a noninvasive plethysmograph (EndoPAT 2000), which is associated with nitric oxide-dependent vasodilatation and yields a peripheral arterial tone (PAT) ratio. RESULTS: Mean systolic pulmonary pressure was 70.5 +/- 21.6 mm Hg (idiopathic-PAH) and 69.3 +/- 20 mm Hg (scleroderma-PAH). AI was higher in scleroderma patients (10.5% +/- 19.6% in healthy controls, 9.0% +/- 21.5% in idiopathic-PAH, 20.1% +/- 19.1% in scleroderma-PAH, and 24.4% +/- 18.9% in scleroderma-controls; nonsignificant). PAT ratio was significantly lower (p < 0.05) than control values in idiopathic-PAH and scleroderma-PAH (PAT ratio: control 2.20 +/- 0.25; idiopathic 1.84 +/- 0.51; scleroderma 1.66 +/- 0.66). AI was not correlated to endothelial dysfunction. There were no differences between the 2 PAH patient groups in age, body mass index, New York Heart Association classification, or 6-min walk test. CONCLUSION: Our study shows a trend towards increased arterial stiffness in scleroderma (nonsignificant), and also peripheral endothelial dysfunction in idiopathic-PAH and in scleroderma-PAH. These findings suggest involvement of different vessels in scleroderma-PAH compared to idiopathic-PAH.

Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug.

Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-year-old woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin) tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis.

Use of Amplatzer device for endobronchial closure of bronchopleural fistulas.

Bronchopulmonary fistula (BPF) is associated with high morbidity and mortality. It occurs as an uncommon but often severe complication of pneumonectomy. BPF may be treated by a range of surgical and medical techniques, including chest drain, Eloesser muscle flap, omental flap, transsternal bronchial closure, thoracoplasty, and prolonged therapy with antibiotic regimens. The use of bronchoscopy has been reported for the delivery of biological glue, coils, covered stents, and sealants. In this work, we describe a novel method of BPF closure using the Amplatzer device, which is commonly used for transcatheter closure of atrial septal defects.

Protective effect of immunosuppression on granulation tissue formation in metallic airway stents.

OBJECTIVES/HYPOTHESIS: The use of self-expanding metallic airway stents has been extended in recent years in inoperable patients with malignant and benign airway diseases. The risk of granulation tissue formation in the stent is a major concern. The objective of the present study was to determine whether immunosuppression modulates granulation tissue formation in airway stents, as seen in coronary stents. STUDY DESIGN: The study included 19 patients with benign airway obstructions and 11 recipients of lung transplants with anastomotic obstructions who were receiving immunosuppression therapy. METHODS: The degree of in-stent granulation tissue formation was evaluated (score range, 0-3) every 3 months for 2 years. RESULTS: Granulation tissue formation was significantly lower in the transplant recipients than in the nontransplant patients at 3 months (score 0.7 vs. 1.6, P = .031), 15 months (score 0 vs. 1.1, P = .026), and 18 months (score 0 vs. 1.8, P = .020). During the 2 years of follow-up, the transplant recipients underwent significantly fewer laser resections and brachytherapy treatments for in-stent granulation. CONCLUSIONS: The immunosuppression given to lung transplant recipients may have an inhibitory effect on granulation tissue formation in metallic airway stents. Further studies are needed to evaluate the effect of systemic therapy or coated stents with drugs such as sirolimus.

Increased erythrocyte adhesiveness and aggregation in obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with an increased incidence of stroke and myocardial infarction as well as increased prothrombotic and inflammatory processes. Although erythrocyte adhesiveness/aggregation is known to be elevated in cardiovascular diseases, it has never been evaluated in OSA. The aim of this study was to examine the possible association of OSA and erythrocyte adhesiveness/aggregation. METHODS: The study was conducted in the Sleep Laboratory of a tertiary university-affiliated medical center in 79 patients (age 57.1+/-12.9 years) with a diagnosis of OSA (apnea hypopnea index 41.2+/-25.9). Findings were compared with data on 1079 controls without clinical symptoms of OSA, matched for sex, age, and body mass index. Overnight polysomnography and blood sampling for erythrocyte sedimentation rate, levels of fibrinogen, high-sensitivity C-reactive protein, and erythrocyte adhesion/aggregation test consisting of measures of erythrocyte percentage and vacuum range on image analysis. RESULTS: The study group had significantly higher values than controls of all three markers of inflammation (p<0.001 for erythrocyte sedimentation rate and fibrinogen; p=0.037 for C-reactive protein). Erythrocyte percentage was significantly lower in the sleep apnea group (84.05+/-15.97 vs. 90.79+/-11.23%, p<0.001), and vacuum range was significantly higher (8.22+/-7.98 vs. 4.63+/-4.05 microm, p<0.001), indicating stronger erythrocyte adhesion/aggregation. Both these factors were significantly correlated with erythrocyte sedimentation rate and to hs-CRP (percentage: r=-0.630; 0.258, p=0.005; 0.031; vacuum range: r=0.494; -0.328, p=0.001; 0.005 respectively). CONCLUSION: OSA is associated with increased erythrocyte aggregation/adhesion, which is correlated with an increase in inflammation markers. These findings might help explain the increased cardiovascular morbidity in OSA.

The association of OSA with insulin resistance, inflammation and metabolic syndrome.

Obstructive sleep apnea (OSA) shares many cardiovascular risk factors with metabolic syndrome, including obesity, hypertension, insulin resistance, and pro-inflammatory state. This study aimed to examine the possible association of OSA severity with insulin resistance, inflammation and the metabolic syndrome. Ninety eight patients suspected for OSA (54.9+/-13.1 years) were studied. Overnight polysomnography and blood sampling was taken for glucose, insulin, high-density lipoprotein(HDL)-cholesterol, triglycerides, high-sensitivity C-reactive protein (Hs-CRP), and serum amyloid A (S-AA). Insulin resistance was estimated by the homeostatic model assessment (HOMA). Each patient was assigned a metabolic score according to the number of discrete components of metabolic syndrome identified, and categorized by OSA severity. Nine patients had primary snoring, nine had mild, 27 moderate and 53 severe OSA. Metabolic score increased from 1.56+/-1.01 to 2.92+/-1.20 with OSA severity (p=0.004), and was correlated independently with apnea hypopnea index (AHI; r=0.432, p=0.001) and with body mass index (BMI; r=0.518 p=0.001). Hs-CRP increased from 3.44+/-4.25 to 5.87+/-4.76mg/dL with OSA severity (p=0.066) and correlated with AHI (r=0.348; p=0.002). Insulin resistance, correlated significantly with AHI (r=0.390 p=0.021). Inflammation, insulin resistance and metabolic syndrome increase with OSA severity. The number of cardinal features of metabolic syndrome increases with an increase in OSA severity, regardless of the BMI.