Exhaled volatile organic compounds for diagnosis and monitoring of asthma.

The asthmatic inflammatory process results in the generation of volatile organic compounds (VOCs), which are subsequently secreted by the airways. The study of these elements through gas chromatography-mass spectrometry (GC-MS), which can identify individual molecules with a discriminatory capacity of over 85%, and electronic-Nose (e-NOSE), which is able to perform a quick onboard pattern-recognition analysis of VOCs, has allowed new prospects for non-invasive analysis of the disease in an "omics" approach. In this review, we aim to collect and compare the progress made in VOCs analysis using the two methods and their instrumental characteristics. Studies have described the potential of GC-MS and e-NOSE in a multitude of relevant aspects of the disease in both children and adults, as well as differential diagnosis between asthma and other conditions such as wheezing, cystic fibrosis, COPD, allergic rhinitis and last but not least, the accuracy of these methods compared to other diagnostic tools such as lung function, FeNO and eosinophil count. Due to significant limitations of both methods, it is still necessary to improve and standardize techniques. Currently, e-NOSE appears to be the most promising aid in clinical practice, whereas GC-MS, as the gold standard for the structural analysis of molecules, remains an essential tool in terms of research for further studies on the pathophysiologic pathways of the asthmatic inflammatory process. In conclusion, the study of VOCs through GC-MS and e-NOSE appears to hold promise for the non-invasive diagnosis, assessment, and monitoring of asthma, as well as for further research studies on the disease.

Short-Term Effect of Cigarette Smoke on Exhaled Volatile Organic Compounds Profile Analyzed by an Electronic Nose.

Breath analysis using an electronic nose (e-nose) is an innovative tool for exhaled volatile organic compound (VOC) analysis, which has shown potential in several respiratory and systemic diseases. It is still unclear whether cigarette smoking can be considered a confounder when analyzing the VOC-profile. We aimed to assess whether an e-nose can discriminate exhaled breath before and after smoking at different time periods. We enrolled 24 healthy smokers and collected their exhaled breath as follows: (a) before smoking, (b) within 5 min after smoking, (c) within 30 min after smoking, and (d) within 60 min after smoking. Exhaled breath was collected by a previously validated method and analyzed by an e-nose (Cyranose 320). By principal component analysis, significant variations in the exhaled VOC profile were shown for principal component 1 and 2 before and after smoking. Significance was higher 30 and 60 min after smoking than 5 min after (p < 0.01 and <0.05, respectively). Canonical discriminant analysis confirmed the above findings (cross-validated values: baseline vs. 5 min = 64.6%, AUC = 0.833; baseline vs. 30 min = 83.6%, AUC = 0.927; baseline vs. 60 min = 89.6%, AUC = 0.933). Thus, the exhaled VOC profile is influenced by very recent smoking. Interestingly, the effect seems to be more closely linked to post-cigarette inflammation than the tobacco-related odorants.

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.

mTOR-Inhibition and COVID-19 in Kidney Transplant Recipients: Focus on Pulmonary Fibrosis.

Kidney transplant recipients are at high risk of developing severe COVID-19 due to the coexistence of several transplant-related comorbidities (e.g., cardiovascular disease, diabetes) and chronic immunosuppression. As a consequence, a large part of SARS-CoV-2 infected patients have been managed with a reduction of immunosuppression. The mTOR-I, together with antimetabolites, have been often discontinued in order to minimize the risk of pulmonary toxicity and to antagonize pharmacological interaction with antiviral/anti-inflammatory drugs. However, at our opinion, this therapeutic strategy, although justified in kidney transplant recipients with severe COVID-19, should be carefully evaluated in asymptomatic/paucisymptomatic patients in order to avoid the onset of acute allograft rejections, to potentially exploit the mTOR-I antiviral properties, to reduce proliferation of conventional T lymphocytes (which could mitigate the cytokine storm) and to preserve Treg growth/activity which could reduce the risk of progression to severe disease. In this review, we discuss the current literature regarding the therapeutic potential of mTOR-Is in kidney transplant recipients with COVID-19 with a focus on pulmonary fibrosis.

Incidence of deep venous thrombosis in patients with both Pulmonary Embolism and COPD.

BACKGROUND: There are no studies investigating populations of patients with both pulmonary embolism and chronic obstructive pulmonary disease (PE-COPD) with and without deep venous thrombosis (DVT). AIM OF THE STUDY: To define prevalence of DVT in COPD with PE and to compare characteristics of COPD patients who develop PE, with and without DVT. Secondly, we aimed to assess differences in the localization of PE among study groups.  METHODS. 116 patients with PE were enrolled in a retrospective study. Clinical data as well as echocardiographic and lower limb ultrasonography records were collected for all subjects. Subjects were divided into two groups according to the presence of COPD: Group 1, 54 patients with diagnosis of PE without COPD and Group 2, 66 patients diagnosed of PE with  COPD. Then, individuals of Group 2 were subdivided in two subgroups according to the presence (n=21) or absence (n=45) of DVT. RESULTS: 33% of patients with COPD and PE showed DVT.  These subjects had higher PaCO2 and ejection fraction (p<0.05 for all) and higher percentage of chronic renal failure and diabetes mellitus compared to those without DVT (p<0.05 for all). Moreover, in COPD-PE patients with DVT, the most frequent localization was proximal (54% of total), whereas COPD-PE patients without DVT showed a more frequent segmental localization (60% of total). No difference was found in clinical presentation and blood-chemistry tests. CONCLUSIONS: DVT was non-common in PE-COPD patients. Chronic renal failure, and type 2 diabetes mellitus are more frequent in PE-COPD patients with DVT, that showed a higher frequency of proximal localization, thereby indicating a greater risk of more severe clinical implications. Conversely, PE- COPD subjects without DVT showed a more frequent segmental localization and were less hypercapnic. PE should be taken into account in COPD with worsening of respiratory symptoms, also in absence of DVT.

Criteria of prescription of antibiotics and systemic corticosteroids among pulmonologists and general practictioners during asthma and COPD exacerbations: a southern Italian survey.

To date, there is still a lack of unanimity regarding the definition of exacerbation of asthma and COPD and about objective measurements in the currently used criteria. The aim of our study was to conduct a survey among general practitioners (GPs) and pulmonologists regarding the clinical criteria arbitrarily considered as important to start a course of systemic corticoids and/or antibiotics in asthma and COPD. We conducted a survey enrolling 50 general practitioners (GPs) and 50 pulmonologists, that evaluated the clinical criteria arbitrated as essential to start a course of systemic corticosteroids or antibiotics during asthma and/or COPD exacerbations. Our results demonstrated incongruities between GPs and pulmonologist and within the same professional category concerning systemic corticosteroids. Conversely, we showed higher consensus between and within the groups about criteria to prescribe antibiotics.

Breathing Rhythm Variations during Wash-In Do Not Influence Exhaled Volatile Organic Compound Profile Analyzed by an Electronic Nose.

E-noses are innovative tools used for exhaled volatile organic compound (VOC) analysis, which have shown their potential in several diseases. Before obtaining a full validation of these instruments in clinical settings, a number of methodological issues still have to be established. We aimed to assess whether variations in breathing rhythm during wash-in with VOC-filtered air before exhaled air collection reflect changes in the exhaled VOC profile when analyzed by an e-nose (Cyranose 320). We enrolled 20 normal subjects and randomly collected their exhaled breath at three different breathing rhythms during wash-in: (a) normal rhythm (respiratory rate (RR) between 12 and 18/min), (b) fast rhythm (RR > 25/min) and (c) slow rhythm (RR < 10/min). Exhaled breath was collected by a previously validated method (Dragonieri et al., J. Bras. Pneumol. 2016) and analyzed by the e-nose. Using principal component analysis (PCA), no significant variations in the exhaled VOC profile were shown among the three breathing rhythms. Subsequent linear discriminant analysis (LDA) confirmed the above findings, with a cross-validated accuracy of 45% (p = ns). We concluded that the exhaled VOC profile, analyzed by an e-nose, is not influenced by variations in breathing rhythm during wash-in.

Galectin-3 and neutrophil-to-lymphocyte ratio are indicative of heart remodelling and disease severity in patients with obstructive sleep apnoea.

BACKGROUND: Galectin-3, considered as a new inflammatory marker; it is increased in cardiovascular disease. We investigated Galectin-3 in relation to heart damage in patients with OSA and its role in inflammation, based on the Neutrophil-to-Lymphocyte Ratio (NLR). METHODS: Sixty-three consecutive patients (45 males, 18 females, 58.60 ± 12.28 years old) were studied. According to the Apnoea-Hypopnoea Index (AHI) patients were divided into Group 1 - non-severe (AHI <30) (17 males and 10 females, 59.89 ± 10.62 years old) and Group 2 - severe (AHI ≥30) (29 males and 6 females, aged 57.53 ± 13.30 years old) OSA. All patients underwent morning blood gas analysis, laboratory tests, nocturnal polygraphy, and echocardiography. RESULTS: Galectin-3 was significantly increased in Group 2 (p = 0.027) patients. Moreover, it was directly related to left ventricle (LV) mass, left ventricle hypertrophy and LV posterior wall diameter. Tissue Doppler septal velocity (e'), that measures wall motion, was inversely correlated to Galectin-3. Furthermore, a direct association to diastolic dysfunction, evaluated as E/e' ratio, was observed. In line with these data, a direct correlation between Galectin-3 and left atrium volume was also found. Galectin-3 and percentage of total registration time with nocturnal oxygen saturation <90% (TST90) were directly correlated (p = 0.0003), while Galectin-3 and mean nocturnal SpO2 were negatively correlated (p = 0.0045). We found a direct correlation between Galectin-3 and NLR (p = 0.011). Finally, Galectin-3 was able to predict 3-yr mortality with a specificity of 83.33% and a sensitivity of 91.84%. CONCLUSION: Galectin-3 showed a direct association to nocturnal respiratory indices and to cardiac remodelling in patients with OSA. OSA-induced inflammation may play an important role in the pathogenesis of heart damage.

Covid-19 and ex-smokers: an underestimated prognostic factor?

Dear Editor, The recent and explosive worldwide outbreak of Covid-19 leads many scientists and clinicians to identify the most responsible triggering risk factors in individuals without comorbidities, as well as potential prognostic factors. A notable field of research has been conducted on the role of smoking, which has been initially hypothesized as being a protective factor for Covid-19....

The importance of maintaining the same order of performance of lung function and SNIP tests in patients with amyotrophic lateral sclerosis.

Objective: Sniff nasal inspiratory pressure (SNIP), a useful tool for the assessment of diaphragm function in patients with Amyotrophic Lateral Sclerosis (ALS), is usually performed together with lung function tests. The aim of this study was to evaluate whether SNIP results are influenced by the order of performance of the tests. Methods: 103 consecutive patients (65% males, 80% spinal onset) were recruited. The highest value of up to 10 sniffs, was recorded before (SNIPT0) and after (SNIPT1) the assessment of lung function, peak cough (PCF), and peak expiratory flow (PEF). Results: Mean and median values were respectively 31.10 and 26.00 cm H2O for SNIPT0 and 28.93 and 25.00 cm H2O for SNIPT1 (p < 0.001). The median value of (SNIPT1 - SNIPT0)/SNIPT0% was -7.10. Patients showing post lung function SNIP values above the median were included in Group 1 (51%), the others in group 2 (49%). Group 2 showed more severe baseline ventilatory restriction and reduction in PCF than Group 1. Positive direct relationships were found between SNIPT0 and SNIPT1 (coefficient ß = 0.95, p < 0.001), and forced vital capacity and forced expiratory volume at one second. Conclusions: 50/103(49%) patients with ALS show a significant reduction in SNIP when assessed shortly after the performance of lung function tests. These patients suffer from more severe ventilatory restriction than patients not showing the reduction. Our findings suggest standardizing the order of respiratory tests during the follow up in order to avoid to misestimate the real strength of inspiratory muscles.

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.

Assessment of Induced Sputum Cellularity in COPD Patients Belonging to Two Different Classes of Air Pollution Exposure / Estudio de la celularidad en el esputo inducido de pacientes con EPOC expuestos a dos niveles diferentes de contaminación atmosférica

INTRODUCTION: Several studies have previously demonstrated that long-term exposure to outdoor pollution present airway inflammation in term of an increase of sputum neutrophils. AIM AND METHODS: The aim of our study was to evaluate the level of airway inflammation by induced sputum in a group of 15 non-professionally exposed population of well-characterized COPD patients, residing in urban areas with high rate of outdoor pollution, compared to a control group of 13 individuals with COPD, living in rural areas with a low pollution rate. All participants underwent spirometry and sputum induction. RESULTS: A statistically significant increase in the percentage of neutrophil cell count was found among the residents in urban areas compared to those living in rural regions (89.1 vs 79.0, p < 0.05). CONCLUSIONS: In conclusion, we showed that non-professionally exposed patients with COPD residing in highly-polluted urban areas had greater airway inflammation in terms of sputum neutrophils compared to a population with very similar characteristics, living in rural areas with lower outdoor pollution. The results of this pilot study may be relevant for the long term effect of environmental outdoor pollution in vulnerable patients like those with COPD

INTRODUCCIÓN: Varios estudios han demostrado con anterioridad que la exposición a la contaminación atmosférica a largo plazo provoca una inflamación de la vía aérea que se ve reflejada en un aumento de neutrófilos en el esputo. OBJETIVO Y MÉTODOS: El objetivo de nuestro estudio fue estimar el grado de inflamación de la vía aérea a través del esputo inducido en un grupo de 15 pacientes con EPOC bien caracterizada sin exposición por motivos profesionales y residentes en áreas urbanas con un nivel alto de contaminación atmosférica, comparados con un grupo control de 13 individuos con EPOC que vivían en zonas rurales con un nivel de contaminación atmosférica bajo. A todos los pacientes se les sometió a una espirometría y a una inducción del esputo. RESULTADOS: Se encontró un aumento estadísticamente significativo en el porcentaje de recuento celular de neutrófilos de los residentes en áreas urbanas en comparación con aquellos que vivían en zonas rurales (89,1 frente a 79,0%, p < 0,05). CONCLUSIONES: En conclusión, demostramos que los pacientes con EPOC que no estaban expuestos debido a su profesión y residentes en áreas urbanas con alta contaminación atmosférica presentaban mayor inflamación de la vía aérea en cuanto al número de neutrófilos en esputo en comparación con una población de características muy similares residente en zonas rurales con menos contaminación atmosférica. El resultado de este estudio piloto podría ser relevante para el efecto a largo plazo de la contaminación atmosférica exterior en pacientes especialmente vulnerables como pueden ser aquellos con EPOC

Assessment of Induced Sputum Cellularity in COPD Patients Belonging to Two Different Classes of Air Pollution Exposure.

INTRODUCTION: Several studies have previously demonstrated that long-term exposure to outdoor pollution present airway inflammation in term of an increase of sputum neutrophils. AIM AND METHODS: The aim of our study was to evaluate the level of airway inflammation by induced sputum in a group of 15 non-professionally exposed population of well-characterized COPD patients, residing in urban areas with high rate of outdoor pollution, compared to a control group of 13 individuals with COPD, living in rural areas with a low pollution rate. All participants underwent spirometry and sputum induction. RESULTS: A statistically significant increase in the percentage of neutrophil cell count was found among the residents in urban areas compared to those living in rural regions (89.1 vs 79.0, p<0.05) CONCLUSIONS: In conclusion, we showed that non-professionally exposed patients with COPD residing in highly-polluted urban areas had greater airway inflammation in terms of sputum neutrophils compared to a population with very similar characteristics, living in rural areas with lower outdoor pollution. The results of this pilot study may be relevant for the long term effect of environmental outdoor pollution in vulnerable patients like those with COPD.

Exhaled breath profiling by electronic nose enabled discrimination of allergic rhinitis and extrinsic asthma.

AIM: To assess whether an e-nose could discriminate between subjects affected by allergic rhinitis with and without concomitant extrinsic asthma, as well as from healthy controls, in terms of exhaled VOC-profile. METHODS: Fourteen patients with Extrinsic Asthma and Allergic Rhinitis (AAR), 14 patients with Allergic Rhinitis without asthma (AR) and 14 healthy controls (HC) participated in a cross-sectional study. Exhaled breath was collected by a standardized method and sampled by an e-nose (Cyranose 320). Raw data were reduced by Principal component analysis and analyzed by canonical discriminant analysis. Cross-validation accuracy (CVA) and Receiver Operating Characteristic(ROC)-curves were calculated. External validation in newly recruited patients (7 AAR, 7 AR and 7 HC) was tested using the previous training model. RESULTS: Breathprints of patients with AR clustered from those with AAR (CVA = 85.7%), as well as HC (CVA = 82.1%). Breathprints from AAR were also separated from those of HC (CVA = 75.0%). External validation confirmed the above findings. CONCLUSIONS: An e-nose can discriminate exhaled breath from subjects with allergic rhinitis with and without extrinsic asthma, which represent two different diseases with partly overlapping features. This supports the view of using breath profiling to diagnose asthma also in patients with allergic rhinitis.

Nocturnal Hypoventilation May Have a Protective Effect on Ischemic Heart Disease in Patients with Obesity Hypoventilation Syndrome.

The importance of nocturnal hypoventilation (nHyp) in the development of cardiovascular comorbidity (CVM) in patients with obesity hypoventilation syndrome (OHS) is controversial. We recently hypothesized that nHyp may have a protective effect on CVM in OHS. The aim of this study was to evaluate the link between nHyp and CVM in patients with OHS. We performed a retrospective analysis of the clinical records of 60 patients with OHS. The initial population was divided into two groups: (1) 31 subjects with OHS and nHyp (nhOHS); (2) 29 individuals with OHS without nHyp (wnhOHS). All patients had also obstructive sleep apnea. Anthropometric data, medical history, electrocardiogram, pulmonary function testing, arterial blood gas test, and sleep recordings were collected. Patients with nhOHS, compared with those wnhOHS, showed higher values of PaCO2 (48.75 ± 3.78 vs. 46.91 ± 2.09 mmHg; p = 0.023), lower percentage of ischemic heart disease (3.2% vs. 20.7%; p = 0.042), higher oxygen desaturation index (ODI; 55.10/h ± 28.76 vs. 38.51/h ± 23.21; p = 0.017), and higher total sleep time (TST90) with SpO2 <90% (53.58% ± 26.90 vs. 25.64% ± 21.67; p = 0.000). Moreover, individuals in the nhOHS group showed a significantly different (p = 0.031) distribution of the three ODI tertiles 0-32/h, 33-72/h, >72/h compared with those in wnhOHS group (19.4% vs. 37%, 41.9% vs. 51.7%, 38.7% vs. 10.3%, respectively). Subsequent discriminant analysis correctly classified nhOHS and wnhOHS in 66.7% of the cases. Ours is the first study analyzing the correlation between nHyp and CVM in patients with OHS. We showed that nHyp in OHS may have a protective effect on cardiovascular morbidity, in particular on ischemic cardiac disease.