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.

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....

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.

In Vitro Identification of New Transcriptomic and miRNomic Profiles Associated with Pulmonary Fibrosis Induced by High Doses Everolimus: Looking for New Pathogenetic Markers and Therapeutic Targets.

The administration of Everolimus (EVE), a mTOR inhibitor used in transplantation and cancer, is often associated with adverse effects including pulmonary fibrosis. Although the underlying mechanism is not fully clarified, this condition could be in part caused by epithelial to mesenchymal transition (EMT) of airway cells. To improve our knowledge, primary bronchial epithelial cells (BE63/3) were treated with EVE (5 and 100 nM) for 24 h. EMT markers (α-SMA, vimentin, fibronectin) were measured by RT-PCR. Transepithelial resistance was measured by Millicell-ERS ohmmeter. mRNA and microRNA profiling were performed by Illumina and Agilent kit, respectively. Only high dose EVE increased EMT markers and reduced the transepithelial resistance of BE63/3. Bioinformatics showed 125 de-regulated genes that, according to enrichment analysis, were implicated in collagen synthesis/metabolism. Connective tissue growth factor (CTGF) was one of the higher up-regulated mRNA. Five nM EVE was ineffective on the pro-fibrotic machinery. Additionally, 3 miRNAs resulted hyper-expressed after 100 nM EVE and able to regulate 31 of the genes selected by the transcriptomic analysis (including CTGF). RT-PCR and western blot for MMP12 and CTGF validated high-throughput results. Our results revealed a complex biological network implicated in EVE-related pulmonary fibrosis and underlined new potential disease biomarkers and therapeutic targets.

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.

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.

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.

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.

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.

An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD.

BACKGROUND: Exhaled breath contains thousands of gaseous volatile organic compounds (VOCs) that may be used as non-invasive markers of lung disease. The electronic nose analyzes VOCs by composite nano-sensor arrays with learning algorithms. It has been shown that an electronic nose can distinguish the VOCs pattern in exhaled breath of lung cancer patients from healthy controls. We hypothesized that an electronic nose can discriminate patients with lung cancer from COPD patients and healthy controls by analyzing the VOC-profile in exhaled breath. METHODS: 30 subjects participated in a cross-sectional study: 10 patients with non-small cell lung cancer (NSCLC, [age 66.4+/-9.0, FEV(1) 86.3+/-20.7]), 10 patients with COPD (age 61.4+/-5.5, FEV(1) 70.0+/-14.8) and 10 healthy controls (age 58.3+/-8.1, FEV(1) 108.9+/-14.6). After 5 min tidal breathing through a non-rebreathing valve with inspiratory VOC-filter, subjects performed a single vital capacity maneuver to collect dried exhaled air into a Tedlar bag. The bag was connected to the electronic nose (Cyranose 320) within 10 min, with VOC-filtered room air as baseline. The smellprints were analyzed by onboard statistical software. RESULTS: Smellprints from NSCLC patients clustered distinctly from those of COPD subjects (cross validation value [CVV]: 85%; M-distance: 3.73). NSCLC patients could also be discriminated from healthy controls in duplicate measurements (CVV: 90% and 80%, respectively; M-distance: 2.96 and 2.26). CONCLUSION: VOC-patterns of exhaled breath discriminates patients with lung cancer from COPD patients as well as healthy controls. The electronic nose may qualify as a non-invasive diagnostic tool for lung cancer in the future.

HPV16 E7-dependent transformation activates NHE1 through a PKA-RhoA-induced inhibition of p38alpha.

BACKGROUND: Neoplastic transformation originates from a large number of different genetic alterations. Despite this genetic variability, a common phenotype to transformed cells is cellular alkalinization. We have previously shown in human keratinocytes and a cell line in which transformation can be turned on and followed by the inducible expression of the E7 oncogene of human papillomavirus type 16 (HPV16), that intracellular alkalinization is an early and essential physiological event driven by the up-regulation of the Na/(+)H(+) exchanger isoform 1 (NHE1) and is necessary for the development of other transformed phenotypes and the in vivo tumor formation in nude mice. METHODOLOGY: Here, we utilize these model systems to elucidate the dynamic sequence of alterations of the upstream signal transduction systems leading to the transformation-dependent activation of NHE1. PRINCIPAL FINDINGS: We observe that a down-regulation of p38 MAPK activity is a fundamental step in the ability of the oncogene to transform the cell. Further, using pharmacological agents and transient transfections with dominant interfering, constitutively active, phosphorylation negative mutants and siRNA strategy to modify specific upstream signal transduction components that link HPV16 E7 oncogenic signals to up-regulation of the NHE1, we demonstrate that the stimulation of NHE1 activity is driven by an early rise in cellular cAMP resulting in the down-stream inhibition of p38 MAPK via the PKA-dependent phosphorylation of the small G-protein, RhoA, and its subsequent inhibition. CONCLUSIONS: All together these data significantly improve our knowledge concerning the basic cellular alterations involved in oncogene-driven neoplastic transformation.

Evaluation of a transcutaneous carbon dioxide monitor in severe obesity.

OBJECTIVE: To determine the reliability of estimating arterial CO(2) pressure (PaCO(2)) using a recently introduced transcutaneous CO(2) pressure (PtcCO(2)) monitor in severe obese patients. DESIGN: Observational and interventional study. SETTING: District hospital with respiratory ward and bariatric surgery unit. PATIENTS AND METHODS: PtcCO(2) was measured in 35 obese patients with varied pathology, including chronic obstructive pulmonary disease, obstructive sleep apnea syndrome and hypoventilation syndrome. Ten minutes after the probe had been attached to an earlobe, PtcCO(2) was recorded immediately before arterial blood sampling. The PtcCO(2) and PaCO(2) values obtained with two methods were compared by Bland-Altman analysis. In a subgroup of 18 obese patients with chronic obstructive pulmonary disease and/or obstructive sleep apnea syndrome with moderate to severe hypercapnia both PtcCO(2) and PaCO(2) were re-evaluated during continuous positive airways pressure (CPAP) or bi-level positive airway pressure (Bi-PAP) treatment. RESULTS: The mean difference between PaCO(2) and PtcCO(2) was -1.4 mmHg, and the standard deviation of the difference was 1.3 mmHg. Bland-Altman analysis showed generally good agreement between the two methods with a 95% limit of agreement of -4 to 1.1. The agreement between methods did not significantly change before and during cPAP or Bi-PAP treatment in hypercapnic patients. CONCLUSIONS: The accuracy of estimation of PaCO(2) by transcutaneous monitoring was generally good in comparison with standard arterial blood gases examination. The device appears to be promising for use in obese patients to evaluate abnormalities in their alveolar ventilation.

A case of cryptogenic organizing pneumonia occurring in Crohn's disease.

A 29 year-old-man with Crohn's disease, who developed diffuse pulmonary infiltrates and hypoxemia two months following oral administration of mesalazine, was examined. Clinical findings and computed tomography were suggestive of, and lung histology was diagnostic of, bronchiolitis obliterans organizing pneumonia, also known as cryptogenic organizing pneumonia. Although the data did not allow for definitive conclusions, they did suggest that the pulmonary disease was an extraintestinal manifestation of Crohn's disease, rather than an adverse reaction to mesalazine. In fact, the patient showed clinical, radiological and functional improvements, despite the treatment with mesalazine and the withdrawal of steroid therapy.

Nuclear factor-kappaB- and glucocorticoid receptor alpha- mediated mechanisms in the regulation of systemic and pulmonary inflammation during sepsis and acute respiratory distress syndrome. Evidence for inflammation-induced target tissue resistance to glucocorticoids.

To test the hypothesis that the interaction between nuclear factor-kappaB (NF-kappaB) and glucocorticoid receptor alpha (GRalpha) is a key pathogenetic mechanism regulating the progression of systemic and pulmonary inflammation in sepsis and acute respiratory distress syndrome (ARDS), we used an ex vivo model of systemic inflammation. Naïve peripheral blood leukocytes (PBL) were exposed to longitudinal (days 1-10) plasma samples from ARDS patients divided into three groups based on physiological improvement and clinical outcome by days 7-10: improvers, nonimprovers-survivors, and nonimprovers-nonsurvivors. In a separate group of nonimprovers-survivors, we correlated the severity of lung histopathology with the intensity of NF-kappaB and GRalpha nuclear staining in immunohistochemistry analysis of lung tissue obtained by open lung biopsy. We found that exposure of naïve cells to longitudinal plasma samples led to divergent directions in NF-kappaB and GRalpha activation that reflected the severity of systemic inflammation. Plasma samples from improvers with declining cytokine levels over time elicited a progressive increase in all measured aspects of glucocorticoid (GC)-induced GRalpha-mediated activity (p = 0.0001) and a correspondent reduction in NF-kappaB nuclear binding (p = 0.0001) and transcription of TNF-alpha and IL-1beta (regulated, GRalpha-driven response). In contrast, plasma samples from nonimprovers with sustained elevation in cytokine levels over time elicited only a modest longitudinal increase in GC-GRalpha-mediated activity (p = 0.04) and a progressive increase in NF-kappaB nuclear binding over time (p = 0.0001) that was most striking in nonsurvivors (dysregulated, NF-kappaB-driven response). By days 3-5, no overlap was observed between groups for NF-kappaB and GC-GRalpha nuclear binding. In immunohistochemistry analyses, lung tissues of patients with severe versus mild ARDS had a higher intensity of NF-kappaB nuclear staining (13 +/- 1.3 vs. 7 +/- 2.9; p = 0.01) and a lower ratio of GRalpha:NF-kappaB in nuclear staining (0.5 +/- 0.2 vs. 1.5 +/- 0.2; p = 0.007). In conclusion, we demonstrated that the ability of GC-GRalpha to downregulate NF-kappaB activation is critical for the resolution of systemic and pulmonary inflammation in ARDS. The findings provide a rationale for the use of prolonged GC treatment in early ARDS.