Reduction of Sniff Nasal Inspiratory Pressure (SNIP) as an Early Indicator of the Need of Enteral Nutrition in Patients with Amyotrophic Lateral Sclerosis.

Percutaneous endoscopic gastrostomy (PEG) is the standard procedure for feeding severely dysphagic patients with amyotrophic lateral sclerosis (ALS). It is associated with prolonged survival and improvement in quality of life. Nasal inspiratory pressure during a sniff (SNIP) is a respiratory test used extensively in ALS for the assessment of inspiratory muscle strength. In this study, we aimed to investigate the role of SNIP at baseline to predict PEG placement in ALS. Data from a clinical incident cohort of 179 ALS cases attending the multidisciplinary ALS unit of the University of Bari between April 2006 and December 2012 were retrospectively analysed. At baseline, patients underwent detailed neurological, nutritional and respiratory assessments, including measurements of SNIP and forced vital capacity (FVC). Patients were therefore followed up approximately every three to six months until they were able to attend the centre. The censoring date for the survival analysis was 15 April 2014, with PEG placement as the main outcome. Cox proportional hazard regression models were used to examine the association between SNIP and PEG placement, adjusted for possible confounders. During the follow-up period, 75 participants (42%) received PEG implant. PEG placement was more frequent (57% vs. 31%; p = 0.001) and earlier (after 11.6 ± 14.0 months from the first visit, vs. 23.3 ± 15.5 months; p < 0.0001) in the group of patients with baseline SNIP ≤ 40 cm H2O. Baseline SNIP was a predictor of PEG placement even after correction for multiple potential confounders (HR 0.98; 95% CI: 0.96-0.99; p = 0.02). To conclude, the present study showed that SNIP at baseline is an early indicator of disease progression and therefore of the need for enteral nutrition in ALS.

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.

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.

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.

Evaluation of endothelial function and cardiovascular risk in non-obese patients with slight degree of obstructive sleep apnea syndrome.

Recently, it has been clearly described an independent relationship between obstructive sleep apnea syndrome (OSAS) and cardiovascular risk, with underlying mechanisms also including endothelial dysfunction. We enrolled 32 consecutive non-obese patients (mean age of 39.5±11.5 years), of which 16 with mild OSAS and 16 snoring without OSAS. Mild OSAS is defined by an AHI index between 5 and 15. We have investigated if whether there was a relationship between mild OSAS, endothelial function and carotid intima-media thickness (C-IMT). The population was divided into two groups: Group 1 (16 simple snorer patients with an average age of 39.4±12.1 years) and Group 2 (16 subjects with mild OSAS with an average age of 39.6±11.2 years). Each group underwent cardiovascular investigation including measurement of flow-mediated dilation (FMD) of the brachial artery and C-IMT. Both groups comprised non-obese subjects. Patients with mild OSAS had serum total cholesterol values statistically significantly higher than simple snores patients (178.6±24.9 vs 159.2±25.3; p=0.038). OSAS patients had also a trend towards higher values of maximum C-IMT compared to simple snorer patients (0.70±0.15 vs 0.65±0.16), although below the level of significance. Between the two groups, no difference was found for FMD values. The present results on mild OSAS strengthen the importance of a diagnosis of OSAS as soon as possible, in order to encourage all primary prevention interventions to correct risk factors responsible for disease progression and the occurrence of cardiovascular diseases, not excluding the use of therapies of non-invasive ventilation even in the early stages of the disease.

Exhaled breath profiling in patients with COPD and OSA overlap syndrome: a pilot study.

The analysis of volatile organic compounds (VOCs) by an electronic nose (e-nose) is a groundbreaking method that provides distinct exhaled molecular patterns in several respiratory and systemic diseases. It has been shown that an e-nose can detect obstructive sleep apnea (OSA) as well as chronic obstructive pulmonary disease (COPD). OSA and COPD are sometimes associated into the so-called overlap syndrome (OVS). In this pilot study we hypothesized that an e-nose could discriminate the exhaled breath of patients with OVS from that of subjects with OSA and COPD alone. Thirteen patients with OSA, 15 patients with COPD and 13 with OVS participated in a cross-sectional study. Exhaled breath was collected by a formerly validated method and sampled by using an electronic nose (Cyranose 320). Raw data were analyzed by canonical discriminant analysis on principal component reduction. Cross-validation accuracy (CVA) and ROC-curves were calculated. External validation in newly recruited patients (6 OSA, 6 OVS and 6 COPD) was tested using the previous training set. Breathprints of patients with OSA clustered distinctly from those with OVS (CVA = 96.2%) as well as those with COPD (CVA = 82.1%). Breathprints from OVS were not significantly separated from those of COPD (CVA = 67.9%). External validation confirmed the above findings. The e-nose can distinguish with high accuracy the exhaled VOC-profile of patients with OSA from those with OVS as well as those with COPD. This warrants future studies to confirm the potential of this technique in the non-invasive detection of sleep apnea.

An electronic nose may sniff out amyotrophic lateral sclerosis.

Amyothrophic lateral Sclerosis (ALS) is a neurodegenerative disease characterized by a progressive degeneration of the cortical and spinal motor neuron. Exhaled molecular profiles that have potential in the diagnosis of several respiratory and systemic diseases can be obtained by analyzing human breath with an electronic nose. We hypothesized that exhaled molecular profiling may discriminate well-characterized patients with ALS from controls. 20 ALS patients (age: 63.5±12.3), and 20 healthy controls (age: 58.1±4.4) participated in a cross-sectional study. A Tedlar bag was used to collect exhaled breath by using a validated method. Bags were then sampled by an electronic nose (Cyranose 320). Statistical analysis on sensor responses was performed off-line by principal component analysis, linear discriminant analysis and ROC curves. Breathprints from patients with ALS were discriminated from healthy controls (CVA: 75.0%; p=0.003; AUC 0.795). Based on our results, patients with ALS can be discriminated from healthy controls. This suggests that exhaled breath analysis has potential for screening and/or diagnosis of this neuromuscular disease.

An electronic nose in the discrimination of obese patients with and without obstructive sleep apnoea.

Exhaled breath contains thousands of volatile organic compounds (VOCs) in gaseous form, which may be used as markers of airway inflammation and lung disease. Electronic noses enable quick and real-time pattern analysis of VOC spectra. It has been shown that the exhaled breath of patients with obstructive sleep apnoea (OSA) differs from that of non-obese controls. We aimed to assess the influence of obesity in the composition of exhaled VOCs by comparing obese subjects with and without OSA. Moreover, we aimed to identify the discriminant VOCs in the two groups.19 obese patients with established OSA (OO; age 51.2 ± 6.8; body mass index (BMI) 34.3 ± 3.5), 14 obese controls without OSA (ONO; age 46.5 ± 7.6; BMI 33.5 ± 4.1) and 20 non-obese healthy controls (HC; age 41.1 ± 12.6; BMI 24.9 ± 3.8) participated in a cross-sectional study. Exhaled breath was collected by a previously described method and sampled by using an electronic nose (Cyranose 320) and by gas chromatography-mass spectrometry (GC-MS) analysis. Breathprints were analyzed by canonical discriminant analysis on principal component reduction. Cross-validation accuracy (CVA) was calculated. Breathprints from the HC group were separated from those of OO (CVA = 97.4%) and ONO (CVA = 94.1%). Breathprints from OO were moderately separated from those of ONO (CVA = 67.6%).The presence of OSA alters the exhaled VOC pattern in obese subjects. The incomplete separation of breathprints between OO and ONO may be due to the same underlying inflammation caused by obesity.

Sniff nasal inspiratory pressure as a prognostic factor of tracheostomy or death in amyotrophic lateral sclerosis.

Forced vital capacity (FVC) shows limitations in detecting respiratory failure in the early phase of amyotrophic lateral sclerosis (ALS). In fact, mild-to-moderate respiratory muscle weakness may be present even when FVC is normal, and ALS patients with bulbar involvement might not be able to perform correctly the spirometry test. Sniff nasal inspiratory pressure (SNIP) is correlated with transdiaphragmatic strength. We evaluated SNIP at baseline as a prognostic factor of tracheostomy or death in patients with ALS. In a multidisciplinary tertiary care center for motorneuron disease, we enrolled 100 patients with ALS diagnosed with El Escorial criteria in the period between January 2006 and December 2010. Main outcome measures were tracheostomy or death. RECursive Partitioning and AMalgamation (RECPAM) analysis was also used to identify subgroups at different risks for the tracheostomy or death. Twenty-nine patients with ALS reached the outcome (12 died and 17 had tracheostomy). Using a multivariate model SNIP correctly classified the risk of the composite event within 1 year of follow-up with a continuous Net Reclassification Improvement cNRI of 0.58 (p = 0.03). Sex, Amyotrophic Lateral Sclerosis Functional Rating Scale revisited, site of onset, and FVC did not improve the classification of prognostic classes. SNIP ≤18 cmH2O identified the RECPAM class with the highest risk (Class 1, hazard ratio = 9.85, 95 % confidence interval: 2.67-36.29, p < 0.001). SNIP measured at baseline identified patients with ALS with initial respiratory failure. Finally, using only ALS patients with spinal onset of the disease, our findings were mostly overlapping with those reported in the models including the whole sample. At baseline, SNIP appeared to be the best predictor of death or tracheostomy within 1 year of follow-up. The measurement of SNIP in the early phase of the disease may contribute to identify patients with high risk of mortality or intubation. SNIP may also provide an additional tool for baseline stratification of patients with ALS in clinical trials.