Early effectiveness of type-2 severe asthma treatment with dupilumab in a real-life setting; a FeNO-driven choice that leads to winning management.

Background: Dupilumab is a humanized monoclonal antibody targeting the IL4/IL13 signaling pathway, already used for atopic dermatitis and chronic rhinitis with nasal polyps, recently approved for severe type-2 asthma. Its efficacy has been demonstrated in randomized control trials. The aim of our study is to evaluate possible early clinical improvement and type 2 biomarkers modifications in severe asthmatic patients treated with dupilumab in a real-life setting. Methods: We included 12 patients with severe, uncontrolled asthma and dupilumab was chosen if there was at least one evidence of blood eosinophils> 150 cells/ml and/or FeNO>25 ppb during last year. Recent blood eosinophil count report, assessment through ACT, FeNO test and spirometry were performed at baseline and after 3 months of treatment. We calculated also the number of patients achieving a minimal, yet clinically relevant difference in FEV1 and ACT. Results: After three months of treatment with dupilumab, ACT had a significant improvement (mean ACT pre 13.25±4.65 vs mean ACT post 19.17±4.45; p<0.01), so as FEV1% (mean FEV1% pre 62.58±15.73 vs mean FEV1% post 71.00±13.11; p<0.01). FeNO had a significant reduction (median FeNO 32 pre, IQR 19-48.5 vs median FeNO19 post, IQR 16.5-26), differently from eosinophils blood count (median eosinophils pre 280, IQR 193.8-647.3 vs median eosinophils post 349.5, IQR 103-836.8; p=0.52). Four patients (33%) had a positive MCID for FEV1, and eight patients (67%) had a positive MCID for ACT. Conclusions: In RCTs performed during clinical development program dupilumab showed an early efficacy in increasing FEV1, reducing FeNO and improving asthma control. Our study demonstrates early improvement in asthmatic symptoms, lung function and FeNO in severe type-2 asthma patients after only 3 months of dupilumab biologic therapy. The introduction of FeNO levels evaluation in the selection criteria for dupilumab, further helps the identification of eligible patients among type-2 severe asthma patients and allows a complete outpatient assessment. Further real-life studies with a longer follow up time will be useful to confirm dupilumab efficacy and to promote its use in clinical practice.

Relationships between Obstructive Sleep Apnea Syndrome and cardiovascular risk in a naïve population of southern Italy.

BACKGROUND: Obstructive sleep apnea (OSA) is a worldwide increasing syndrome, which, by promoting endothelial dysfunction, contributes to extend the cardiovascular risk. We evaluated the cardiovascular risk in a group of OSA patients. METHODS: A total of 185 OSA subjects (19 normal weight, 57 overweight, 109 obese), who entered the Ambulatory of Sleep Disorders of the Institute of Respiratory Diseases of the University of Bari, during 1 year, were enrolled in the study. We assessed anthropometric features, polysomnographic findings, cardiovascular risk factors, smoking habit, Pulmonary Function Test, Arterial Blood Gas Analysis, Epworth Questionnaire, and Charlson Co-morbidities Index (CCI). Subjects were divided into three groups, according to their BMI: individuals with BMI ≥30 kg/m2 (Group 1 n = 109, mean age 61 ± 1; 74.3% men), individuals with BMI ranging from 25.0 to 29.9 kg/m2 defined as overweight subjects (Group 2 n = 57, mean age 58.8 ± 1.4; 77% men), and subjects with a BMI ranging from 18.5 to 24.9 kg/m2 defined as normal weight subjects (Group 3 n = 19, mean age 54.2 ± 2.3; 64,2% men). RESULTS: In the whole population, the percentage cardiovascular risk was weakly related with BMI (r = 0.33; P < .001), but not with AHI. The cardiovascular risk was strictly related to the obesity (P < .00002), while the Epworth Questionnaire score and the Charlson Co-morbidity Index were respectively statistically higher in the group of obese individuals (P = .004, P = .0002) than in the other two sub-groups. When AHI values were stratified in tertiles, the percentage cardiovascular risk did not vary with increasing AHI values (Figure 2). CONCLUSIONS: Further studies are required to investigate the pivotal role of inflammation resulting from obesity, and underlying increased cardiovascular risk in OSA patients.

Impact of smoking, COPD and comorbidities on the mortality of COVID-19 patients.

The prognosis of the coronavirus disease 2019 (COVID-19) patients is variable and depends on several factors. Current data about the impact of chronic obstructive pulmonary disease (COPD) and smoking on the clinical course of COVID-19 are still controversial. This study evaluated the prevalence and the prognosis of COPD patients and smokers in a cohort of 521 patients admitted to four intermediate Respiratory Intensive Care Units (Puglia, Italy) with respiratory failure due to COVID-19 pneumonia. The prevalence of COPD and current smokers was 14% and 13%, respectively. COPD patients had a higher 30-day all-cause mortality than non-COPD patients. Former smokers compared to never smokers and current smokers had higher 30-day all-cause mortality. COPD patients and former smokers had more comorbidities. This study described the prevalence and the outcomes of COPD patients and smokers in a homogenous cohort of COVID-19 patients. The study showed that the prevalence of COPD and current smokers was not high, suggesting that they were not at increased risk of getting the infection. However, when SARS-CoV-2 infection occurred, COPD patients and former smokers were those with the highest all-cause mortality, which seemed to be mainly related to the presence of comorbidities and not to COPD and smoking itself.

Hemoptysis due to a large endobronchial mass successful regression after the use of high flow nasal cannula.

In recent years, high flow nasal cannula is being increasingly used. Most studies showed positive results when used in hypoxaemic respiratory failure. Its use in a patient with a large endobronchial mass has not yet being described. We report a patient who presented with hemoptysis and hypoxaemic respiratory failure second to a large mass obstructing the right main bronchus. High flow oxygen via nasal cannula was initiated with a quick improvement of the hemoptysis and the oxygen saturation. Thus, allowing the patient to be rapidly stabilized.

Exhaled volatile organic compounds analysis by e-nose can detect idiopathic pulmonary fibrosis.

The current diagnostic work-up and monitoring of idiopathic pulmonary fibrosis (IPF) is often invasive and time consuming. Breath analysis by e-nose technology has shown potential in the diagnosis of numerous respiratory diseases. In this pilot study, we investigated whether exhaled breath analysis by an e-nose could discriminate among patients with IPF, healthy controls and COPD. Second, we verified whether these classification could be repeated in a set of newly recruited patients as external validation. Third, we evaluated any significant relationships between exhaled VOCs and Bronchoalveolar lavage fluid (BALF) in IPF patients. We enrolled 32 patients with well-characterized IPF, 33 individuals with COPD and 36 healthy controls. An electronic nose (Cyranose 320) was used to analyze exhaled breath samples. Raw data were processed by Principal component reduction and linear discriminant analysis. External validation in newly recruited patients (10 IPF, 10 COPD and 10 controls) was tested using the previous training set. Exhaled VOC-profiles of patients with IPF were distinct from those of healthy controls (CVA = 98.5%) as well as those with COPD (CVA = 80.0%). External validation confirmed the above findings (IPF vs COPD vs healthy controls, CVA 96.7%). Moreover, a significant inversely proportional correlation was shown between BALF total cell count and both Principal Components 1 and 2 (r = 0.543, r2 = 0.295, p < 0.01; r = 0.501, r2 = 0.251; p < 0.01, respectively). The exhaled breath Volatile Organic Compounds- profile of patients with IPF can be detected by an electronic nose. This suggests that breath analysis has potential for diagnosis and/or monitoring of IPF.

Treatment response according to small airways disease status: The effects of high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate in fixed dose combination in moderate uncontrolled asthmatic patients.

BACKGROUND: Inflammation in small airways is particularly clinically active in severe asthma but they still continue to be ignored as considered silent. Recently, the Atlantis study reports small airways involvement in 91% of the asthma population. Therefore in the era of phenotype driven therapy, the aim of this study was to verify if high-strength extrafine ICS/LABA in fixed dose increases clinical efficacy in moderate asthmatic patients with small airways dysfunction and it could be proposed as phenotype driven therapy. METHODS: In this prospective, non-interventional, real-life pilot study we enrolled 37 consecutive patients with moderate asthma who were uncontrolled despite GINA step 3 treatment. All subjects at enrollment were divided in two groups according to the presence of small airways dysfunction:1) small airways phenotype (SAP) group: smokers (≥10 packs/die), ex-smokers (>20 packs/year) with air trapping (FVC <80% - VR >100% - FEF 25-75%<60%); 2) non-small airways phenotype (NSAP) group: non-smokers, without air trapping (FVC ≥80% - VR ≤ 100% - FEF 25-75%≥60%). We later proceeded in both groups with a step up in therapy with high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate (BDP/FF) (200/6 µg) in fixed dose to achieve a better control and followed patients for 6 months. RESULTS: Treatment with extrafine BDP/FF(200/6 µg) in SAP group showed a more significant improvement of FEF25-75%, FVC, RV, and a reduction of alveolar inflammatory markers such as FENO350 and alveolar exhaled pH compared with NSAP patients. CONCLUSIONS: Our preliminary results support the use of high-strength extrafine pMDI BDP/FF (200/6 µg) as phenotype driven treatment directed to small airways dysfunction demonstrating an increase of clinical efficacy in moderate asthmatics with SAP.

The ovarian cycle may influence the exhaled volatile organic compound profile analyzed by an electronic nose.

INTRODUCTION: We aimed to investigate whether the sex hormone profile during the ovarian cycle in healthy women could affect the volatile organic compound (VOC) profile analyzed by an electronic nose (e-nose). METHODS: We enrolled 21 healthy, never-smoking, regularly menstruating women who were not taking any medications. A series of exhaled breath measurements were performed on all subjects at predefined intervals (days 1-6, 7-12, 13-19, 20-25 and 26-31; day 1 was the first day of menstruation) during their ovarian cycle and analyzed by an e-nose (Cyranose 320). RESULTS: By principal component analysis, significant modifications of the exhaled VOC profile were observed over the cycle for principal component 1 (PC1; p = 0.001). In particular, the PC1 value was significantly higher during the premenstrual period and during menstruation compared with the first third of estrogen phase, mid-cycle and the first third of progestational phase (for all parameters p < 0.05 and p < 0.01, respectively). Subsequent linear discriminant analysis confirmed the above findings. CONCLUSIONS: The ovarian cycle may alter the exhaled VOC pattern and this should be taken into account during serial measurements of these markers in the female population.

Metabolic syndrome and Chronic Obstructive Pulmonary Disease (COPD): The interplay among smoking, insulin resistance and vitamin D.

BACKGROUND: A close relationship between Metabolic Syndrome (MetS) and Chronic Obstructive Pulmonary Disease (COPD) has been described, but the exact nature of this link remains unclear. Current epidemiological data refer exclusively to the MetS prevalence among patients with COPD and data about the prevalence of COPD in MetS patients are still unavailable. AIM OF THE STUDY: To analyse and compare risk factors, clinical and metabolic characteristics, as well as the main respiratory function parameters, among patients affected by MetS, COPD or both diseases. PATIENTS: We recruited 59 outpatients with MetS and 76 outpatients with COPD. After medical history collection, physical examination, blood sampling for routine analysis, spirometric evaluation, they were subdivided into MetS (n = 46), MetS+COPD (n = 60), COPD (n = 29). RESULTS: A MetS diagnosis was assigned to 62% of COPD patients recruited in the COPD Outpatients Clinic of the Pneumology Department, while the COPD prevalence in MetS patients enrolled in the Internal Medicine Metabolic Disorders Outpatients Clinic was 22%. More than 60% of subjects enrolled in each Department were unaware that they suffered from an additional disease. MetS+COPD patients exhibited significantly higher C-peptide levels. We also found a positive relation between C-peptide and pack-years in all subjects and a negative correlation between C-peptide and vitamin D only in current smokers. Finally, a negative association emerged between smoking and vitamin D. CONCLUSIONS: We have estimated, for the first time, the COPD prevalence in MetS and suggest a potential role of smoking in inducing insulin resistance. Moreover, a direct effect of smoking on vitamin D levels is proposed as a novel mechanism, which may account for both insulin resistance and COPD development.

Correction of intermittent hypoxia reduces inflammation in obese subjects with obstructive sleep apnea.

BACKGROUND: In obese subjects with obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) may be linked to systemic and adipose tissue inflammation. METHODS: We obtained abdominal subcutaneous adipose tissue biopsies from OSA and non-OSA obese (BMI > 35) subjects at baseline and after 24 weeks (T1) of weight-loss intervention plus continuous positive airway pressure (c-PAP) or weight-loss intervention alone, respectively. OSA subjects were grouped according to good (therapeutic) or poor (subtherapeutic) adherence to c-PAP. RESULTS: At baseline, anthropometric and metabolic parameters, serum cytokines, and adipose tissue mRNA levels of obesity-associated chemokines and inflammatory markers were not different in OSA and non-OSA subjects. At T1, body weight was significantly reduced in all groups. Serum concentrations of IL-2, IL-4, IL-6, MCP-1, PDGFß, and VEGFα were reduced by therapeutic c-PAP in OSA subjects and remained unaltered in non-OSA and subtherapeutic c-PAP groups. Similarly, adipose tissue mRNA levels of macrophage-specific (CD68, CD36) and ER stress (ATF4, CHOP, ERO-1) gene markers, as well as of IL-6, PDGFß, and VEGFα, were decreased only in the therapeutic c-PAP group. CONCLUSION: CIH does not represent an additional factor increasing systemic and adipose tissue inflammation in morbid obesity. However, in subjects with OSA, an effective c-PAP therapy improves systemic and obesity-associated inflammatory markers. FUNDING: Ministero dell'Università e della Ricerca and Progetti di Rilevante Interesse Nazionale.

Voluntary lung function screening to reveal new COPD cases in southern Italy.

BACKGROUND: Underdiagnosis of COPD is a relevant issue, and most frequently involves patients at early stages of the disease. Physicians do not routinely recommend smokers to undergo spirometry, unless they are symptomatic. AIMS: To investigate the effectiveness of voluntary lung function screening in bringing to light patients with previously unknown COPD and to evaluate the relationships among symptoms, smoking status, and airway obstruction. METHODS: A voluntary screening study for COPD was conducted during two editions of the annual Fiera del Levante (2014 and 2015), an international trade fair in Bari. Subjects were eligible for the study if they fulfilled the following inclusion criteria: age ≥35 years, smoker/ex-smoker ≥5 pack-years (PYs), or at least one chronic respiratory symptom (cough, sputum production, shortness of breath, and wheezing). A free post-ß2-agonist spirometry test was performed by trained physicians for each participant using portable spirometers. Post-ß2-agonist forced expiratory volume in 1 second (FEV1):forced vital capacity ratio <0.7 was chosen to establish the diagnosis of COPD. Sensitivity, specificity, and negative and positive predictive values (NPVs and PPVs) of symptoms for the presence of obstruction were calculated. RESULTS: A total of 1,920 individuals were eligible for the study; 188 subjects (9.8%) met COPD criteria. There was a 10.4% prevalence of COPD in subjects with one or more symptoms who had never smoked or smoked ≤5 PYs. Among COPD patients, prevalence of symptoms increased in the presence of FEV1 <80%. COPD smokers were more symptomatic than smokers without COPD. Sensitivity and specificity in all subjects with one or more symptoms were 87% and 32%, respectively, whereas in smoker subgroups, sensitivity and specificity were 71% and 41% (≥5 PYs) and 74% and 35% (≥10 PYs), respectively. In all subjects, the presence of at least one symptom was associated with a low PPV for COPD of 11%, but a very high NPV (96%). These data did not change if the analysis was limited to smokers. CONCLUSION: Voluntary public lung function screening programs in Italy are effective, and may detect a large number of undiagnosed subjects with COPD in early stages. In our population, COPD symptoms had low specificity and PPV, even considering smokers only.

Electronic Nose Technology in Respiratory Diseases.

Electronic noses (e-noses) are based on arrays of different sensor types that respond to specific features of an odorant molecule, mostly volatile organic compounds (VOCs). Differently from gas chromatography and mass spectrometry, e-noses can distinguish VOCs spectrum by pattern recognition. E-nose technology has successfully been used in commercial applications, including military, environmental, and food industry. Human-exhaled breath contains a mixture of over 3000 VOCs, which offers the postulate that e-nose technology can have medical applications. Based on the above hypothesis, an increasing number of studies have shown that breath profiling by e-nose could play a role in the diagnosis and/or screening of various respiratory and systemic diseases. The aim of the present study was to review the principal literature on the application of e-nose technology in respiratory diseases.

Most Italians attending a congress on health of elderly people do not know and do not recognize respiratory diseases.

BACKGROUND: The present study reports the results of a survey jointly carried out by three Italian respiratory scientific associations (AIMAR, AIPO, SIMeR) together with an important Federation of elderly patients (FederAnziani) during the National Conference of Italian Court for Health Right held in Rimini from November 29(th) to December 1(st), 2013. The survey, based on a spirometric examination preceded by a questionnaire on respiratory health, was conducted on elderly people coming from all Italian regions to attend the Conference. METHODS: Nine hundred forty-nine subjects (574 females and 375 males), mean age 66.2 ± 10.1 years, were interviewed and performed spirometric examination. There were 137 smokers (14.4 %). Mean value of Body Mass Index (BMI) was significantly higher in males (27.6 ± 6.6) than in females (26.3 ± 4.3). RESULTS: 17.1 % (N = 143) of the studied subjects reported to be suffering from respiratory disease and the prevalent illnesses were asthma (31.5 %) and COPD/emphysema (24.5 %), but only 3.3 % of the whole surveyed group was able to identify COPD as a pulmonary disease, however without knowing its characteristics, while these were known by 0.5 % of the interviewed subjects only. A high number of subjects, 22 % of whom were smokers, declared chronic sputum production. 10.2 % of the study group showed an obstructive defect at spirometry when the criterium of lower limit of the normal (LLN) was considered, whereas it was 12.4 % if the fixed limit of 0.70 was chosen. 64 % of the obstructed people thought they did not have any respiratory disease. CONCLUSIONS: The results of this survey, able to spread the knowledge of respiratory diseases and spirometry in a wide sample of subjects for the most part scarcely aware of them, emphasize the need for a greater divulgation of respiratory issues among the general population.

Everolimus-induced epithelial to mesenchymal transition (EMT) in bronchial/pulmonary cells: when the dosage does matter in transplantation.

BACKGROUND: Everolimus (EVE) is a mammalian target of rapamycin inhibitor (mTOR-I) widely used in transplantation that may determine some severe adverse events, including pulmonary fibrosis. The pathogenic mechanism of mTOR-I-associated pulmonary toxicity is still unclear, but epithelial to mesenchymal transition (EMT) of bronchial/pulmonary cells may play a role. METHODS: Three cell lines-human type II pneumocyte-derived A549, normal bronchial epithelial, and bronchial epithelial homozygous for the delta F508 cystic fibrosis-causing mutation-were treated with EVE or tacrolimus at different concentrations. Real-time polymerase chain reaction and immunofluorescence were used to evaluate mRNA and protein levels of EMT markers (alpha-SMA, vimentin, fibronectin). Subsequently, in 13 EVE- and 13 tacrolimus-treated patients we compared the rate of lung fibrosis, estimated by an arbitrary pulmonary fibrosis index score (PFIS). RESULTS: Biomolecular experiments demonstrated that high doses of EVE (100 nM) up-regulated EMT markers in all cell lines at both gene- and protein level. High concentrations of EVE were also able to reduce the mRNA levels of epithelial markers (E-cadherin and ZO-1) and to induce the phosphorylation of AKT. In the in vivo part of the study, PFIS was significantly higher in the EVE-group than the tacrolimus-group (p = 0.03) and correlated with trough levels (R2 = 0.35). CONCLUSIONS: Our data reveal, for the first time, a dose-dependent EVE-induced EMT in airway cells. They suggest that clinicians should employ, wherever possible, low dosages of mTOR-Is in transplant recipients, assessing periodically their pulmonary function.

Pulmonary alveolar microlithiasis: review of the 1022 cases reported worldwide.

Pulmonary alveolar microlithiasis (PAM) is a rare disease characterised by the widespread intra-alveolar accumulation of minute calculi called microliths. It is caused by mutation of the SLC34A2 gene encoding the type IIb sodium phosphate cotransporter in alveolar type II cells. The present study explores the epidemiological, familial, genetic, clinical, diagnostic, radiological and therapeutic aspects with the aim of contributing to a better understanding of this uncommon disease.We searched articles on PAM published up to December 2014 and 544 papers were found, accounting for 1022 cases.PAM is present in all continents and in many nations, in particular in Turkey, China, Japan, India, Italy and the USA. Familiality is frequent. The clinical course is not uniform and the causes of this clinical variability seem to be largely nongenetic. The optimal diagnostic procedure is the association of chest high-resolution computed tomography (HRCT) with bronchoalveolar lavage, but a chest radiograph may suffice in families in which a case has already been diagnosed. Moreover, chest radiography and HRCT allow the classification of the evolutionary phase of the disease and its severity. At present lung transplantation is the only effective therapy. However, better knowledge of the gene responsible offers hope for new therapies.

Smoking Habit in Severe Obese after bariatric procedures.

BACKGROUND: Bariatric procedures provide an effective means of short term weight loss and sustained weight control for the morbidly obese. The effect of bariatric procedures on smoking habit in obese subjects is not well known. Therefore, we examined the short term effect of bariatric surgery on smoking habit of severe obese patients up to 12 months from the intervention. PATIENTS AND METHODS: Smoking habit was assessed in a cohort of 78 morbid smoking obese patients followed at our clinic for bariatric procedures. They underwent non surgical intra-gastric balloon (IB) or surgical procedures such as lap-band laparoscopic surgery (LAGB) or sleeve gastrectomy/gastric by-pass (SPG). Subjects were administered a written questionnaire about their smoking habit before and 3, 6 and 12 months after the procedures. RESULTS: No differences were found among the three groups at 6 and 12 months after the procedures (IB 21 %, LAGB 6 %, SPG 5 %; and IB 14 %, LAGB 3 %, SPG 5 %). Only after 3 months, the rate of quitting of the IB group was higher than LAGB and SPG groups (36 %, 6 % and 5 %, respectively; p = 0.02). CONCLUSIONS: Bariatric procedures have no effects on smoking habit of moderate-to-heavy smoker severe obese patients. The use of other traditional smoking cessation methods in patients undergone to bariatric procedures should be implemented.

Correlation between inflammatory markers of atherosclerosis and carotid intima-media thickness in Obstructive Sleep Apnea.

Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder associated with the development of cardiovascular diseases and atherosclerosis. Systemic inflammation plays an important role in the development of cardiovascular complications in OSA patients. The aim of the study was to evaluate the relationship between carotid intima-media thickness (cIMT) and inflammatory markers plasma levels in OSA patients. We enrolled 80 OSA patients and 40 controls matched for age and body mass index (BMI). The presence and severity of sleep apnea was determined by in-laboratory portable monitoring (PM). Demographic data, blood pressure, heart rate, and cIMT were measured. High-sensitive C-Reactive Protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and pentraxin (PTX)-3 serum concentrations were detected. cIMT was higher in OSA patients than controls (0.89 ± 0.13 mm vs. 0.65 ± 0.1 mm, p < 0.01). Moderate-severe OSA patients (0.95 ± 0.09 mm) had significantly increased cIMT than mild OSA (0.76 ± 0.1 mm; p < 0.01) and control (0.65 ± 0.1 mm; p < 0.01). hsCRP, IL-6, TNF-α, and PTX-3 in patients with OSA (1.67 ± 0.66 mg/L, 2.86 ± 1.39 pg/mL, 20.09 ± 5.39 pg/mL, 2.1 ± 0.59 ng/mL, respectively) were significantly higher than in controls (1.08 ± 0.53 mg/L, p < 0.01; 1.5 ± 0.67 pg/mL, p < 0.01; 12.53 ± 3.48 pg/mL, p < 0.01; 1.45 ± 0.41 ng/mL, p < 0.01, respectively). Carotid IMT was significantly correlated to CRP (r = 0.44; p < 0.01), IL-6 (r = 0.42; p < 0.01), TNF-α (r = 0.53; p < 0.01), and PTX-3 (r = 0.49; p < 0.01). OSA patients showed increased cIMT, CRP, IL-6, TNF-α, and PTX-3 levels. Inflammatory markers levels are correlated to cIMT in OSA patients.

An electronic nose discriminates exhaled breath of patients with untreated pulmonary sarcoidosis from controls.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown cause that affects the lungs in over 90% of cases. Breath analysis by electronic nose technology provides exhaled molecular profiles that have potential in the diagnosis of several respiratory diseases. OBJECTIVES: We hypothesized that exhaled molecular profiling may distinguish well-characterized patients with sarcoidosis from controls. To that end we performed electronic nose measurements in untreated and treated sarcoidosis patients and in healthy controls. METHODS: 31 sarcoidosis patients (11 patients with untreated pulmonary sarcoidosis [age: 48.4 ± 9.0], 20 patients with treated pulmonary sarcoidosis [age: 49.7 ± 7.9]) and 25 healthy controls (age: 39.6 ± 14.1) participated in a cross-sectional study. Exhaled breath was collected twice using a Tedlar bag by a standardized method. Both bags were then sampled by an electronic nose (Cyranose C320), resulting in duplicate data. Statistical analysis on sensor responses was performed off-line by principal components (PC) analyses, discriminant analysis and ROC curves. RESULTS: Breathprints from patients with untreated pulmonary sarcoidosis were discriminated from healthy controls (CVA: 83.3%; AUC 0.825). Repeated measurements confirmed those results. Patients with untreated and treated sarcoidosis could be less well discriminated (CVA 74.2%), whereas the treated sarcoidosis group was undistinguishable from controls (CVA 66.7%) CONCLUSION: Untreated patients with active sarcoidosis can be discriminated from healthy controls. This suggests that exhaled breath analysis has potential for diagnosis and/or monitoring of sarcoidosis.

Recurrent pulmonary embolism due to echinococcosis secondary to hepatic surgery for hydatid cysts.

We describe the case of a 53-year-old man with recurrent pulmonary embolism due to intra-arterial cysts from Echinococcus. Both the patient's medical history and the computed tomographic (CT) scan abnormalities led to the diagnosis. The CT scan, performed during hospitalization in our ward, showed cystic masses in the left main pulmonary artery and in the descending branch of the right pulmonary artery. Within cystic masses, thin septa were visible, giving a chambered appearance, which was suggestive of a group of daughter cysts. In the past, our patient underwent multiple operations for recurring echinococcal cysts of the liver. After the last intervention, 4 years earlier, his postoperative course was complicated by pulmonary embolism: a CT scan showed a filling defect in the descending branch of the right pulmonary artery, which was caused by the same cystic mass as 4 years later, although smaller. This mass, not properly treated, increased in diameter. Moreover, after 4 years, there has been a new episode of embolism, which involved the left main pulmonary artery. This is the first case in which there are repeated episodes of pulmonary embolism echinococcosis after hepatic surgery for removal of hydatid cysts.

An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls.

BACKGROUND: Malignant Pleural Mesothelioma (MPM) is a tumour of the surface cells of the pleura that is highly aggressive and mainly caused by asbestos exposure. Electronic noses capture the spectrum of exhaled volatile organic compounds (VOCs) providing a composite biomarker profile (breathprint). OBJECTIVE: We tested the hypothesis that an electronic nose can discriminate exhaled air of patients with MPM from subjects with a similar long-term professional exposure to asbestos without MPM and from healthy controls. METHODS: 13 patients with a histology confirmed diagnosis of MPM (age 60.9±12.2 year), 13 subjects with certified, long-term professional asbestos exposure (age 67.2±9.8), and 13 healthy subjects without asbestos exposure (age 52.2±16.2) participated in a cross-sectional study. Exhaled breath was collected by a previously described method and sampled by an electronic nose (Cyranose 320). Breathprints were analyzed by canonical discriminant analysis on principal component reduction. Cross-validated accuracy (CVA) was calculated. RESULTS: Breathprints from patients with MPM were separated from subjects with asbestos exposure (CVA: 80.8%, sensitivity 92.3%, specificity 85.7%). MPM was also distinguished from healthy controls (CVA: 84.6%). Repeated measurements confirmed these results. CONCLUSIONS: Molecular pattern recognition of exhaled breath can correctly distinguish patients with MPM from subjects with similar occupational asbestos exposure without MPM and from healthy controls. This suggests that breathprints obtained by electronic nose have diagnostic potential for MPM.