Mobile Health for Central Sleep Apnea Screening Among Patients With Stable Heart Failure: Single-Cohort, Open, Prospective Trial.

BACKGROUND: Polysomnography is the gold standard for detection of central sleep apnea in patients with stable heart failure. However, this procedure is costly, time consuming, and a burden to the patient and therefore unsuitable as a screening method. An electronic health (eHealth) app to measure overnight oximetry may be an acceptable screening alternative, as it can be automatically analyzed and is less burdensome to patients. OBJECTIVE: This study aimed to assess whether overnight pulse oximetry using a smartphone-compatible oximeter can be used to detect central sleep apnea in a population with stable heart failure. METHODS: A total of 26 patients with stable heart failure underwent one night of both a polygraph examination and overnight saturation using a smartphone-compatible oximeter. The primary endpoint was agreement between the oxygen desaturation index (ODI) above or below 15 on the smartphone-compatible oximeter and the diagnosis of the polygraph. RESULTS: The median age of patients was 66.4 (interquartile range, 62-71) years and 92% were men. The median body mass index was 27.1 (interquartile range, 24.4-30.8) kg/m2. Two patients were excluded due to incomplete data, and two other patients were excluded because they could not use a smartphone. Seven patients had central sleep apnea, and 6 patients had obstructive sleep apnea. Of the 7 (of 22, 32%) patients with central sleep apnea that were included in the analysis, 3 (13%) had an ODI≥15. Of all patients without central sleep apnea, 8 (36%) had an ODI<15. The McNemar test yielded a P value of .55. CONCLUSIONS: Oxygen desaturation measured by this smartphone-compatible oximeter is a weak predictor of central sleep apnea in patients with stable heart failure.

A longitudinal study of allergy and intestinal helminth infections in semi urban and rural areas of Flores, Indonesia (ImmunoSPIN Study).

BACKGROUND: The prevalence of asthma and atopic disease has been reported to be low in low income countries, however helminth infections are likely to be high among these communities. The question of whether helminth infections play a role in allergic diseases can best be addressed by intervention studies. None of the studies so far have been based on a large scale placebo-controlled trial. METHOD/DESIGN: This study was designed to assess how intestinal helminth infections can influence the immune response and atopic and allergic disorders in children in Indonesia. The relations between allergic outcomes and infection and lifestyle factors will be addressed. This study was set up among school-age children in semi urban and rural areas, located in Ende District of Flores Island, Indonesia. A randomized placebo-controlled anthelmintic treatment trial to elucidate the impact of helminth infections on the prevalence of skin prick test (SPT) reactivity and symptoms of allergic diseases will be performed. The children living in these semi-urban and rural areas will be assessed for SPT to allergens before and after 1 and 2 years of treatment as the primary outcome of the study; the secondary outcome is symptoms (asthma and atopic dermatitis); while the tertiary outcome is immune responses (both antibody levels to allergens and cellular immune responses). DISCUSSION: The study will provide information on the influence of helminth infections and anthelmintic treatment on immune response, atopy and allergic disorders. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: ISRCTN83830814.

Comparison of exhaled breath condensate pH using two commercially available devices in healthy controls, asthma and COPD patients.

BACKGROUND: Analysis of exhaled breath condensate (EBC) is a non-invasive method for studying the acidity (pH) of airway secretions in patients with inflammatory lung diseases. AIM: To assess the reproducibility of EBC pH for two commercially available devices (portable RTube and non-portable ECoScreen) in healthy controls, patients with asthma or COPD, and subjects suffering from an acute cold with lower-airway symptoms. In addition, we assessed the repeatability in healthy controls. METHODS: EBC was collected from 40 subjects (n = 10 in each of the above groups) using RTube and ECoScreen. EBC was collected from controls on two separate occasions within 5 days. pH in EBC was assessed after degasification with argon for 20 min. RESULTS: In controls, pH-measurements in EBC collected by RTube or ECoScreen showed no significant difference between devices (p = 0.754) or between days (repeatability coefficient RTube: 0.47; ECoScreen: 0.42) of collection. A comparison between EBC pH collected by the two devices in asthma, COPD and cold patients also showed good reproducibility. No differences in pH values were observed between controls (mean pH 8.27; RTube) and patients with COPD (pH 7.97) or asthma (pH 8.20), but lower values were found using both devices in patients with a cold (pH 7.56; RTube, p < 0.01; ECoScreen, p < 0.05). CONCLUSION: We conclude that pH measurements in EBC collected by RTube and ECoScreen are repeatable and reproducible in healthy controls, and are reproducible and comparable in healthy controls, COPD and asthma patients, and subjects with a common cold.

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.

Enhanced airway dilation by positive-pressure inflation of the lungs compared with active deep inspiration in patients with asthma.

Deep inspiration temporarily reduces induced airways obstruction in healthy subjects. This bronchodilatory effect of deep inspiration is impaired in asthma. Passive machine-assisted lung inflation may augment bronchodilation compared with an active deep inspiration in patients with asthma by either opening closed airways or by reducing fluid flux across the airway wall during deep inspiration, and thereby increasing the tethering forces on the airway wall. We recruited 24 patients with asthma [18-46 yr old, forced expiratory volume in 1 s (FEV(1)) > 70% predicted; provocative concentration of methacholine inducing a 20% fall in FEV(1) (PC(20)) < 8 mg/ml], with either an impaired (n = 12) or an intact (n = 12) bronchodilatory response to deep inspiration. Two methacholine challenges were performed on separate days. At a 50% increase in respiratory resistance (forced oscillation technique at 8 Hz), the change in resistance by a positive-pressure inflation (computer-driven syringe) or an active deep inspiration was measured in randomized order. The reduction in resistance by positive-pressure inflation was significantly greater than by active deep inspiration in the impaired deep inspiration response group (mean change +/- SE: -0.6 +/- 0.1 vs. -0.03 +/- 0.2 cmH(2)O.l(-1).s, P = 0.002). No significant difference was found between positive-pressure inflation and active deep inspiration in the intact deep inspiration response group (-0.6 +/- 0.2 vs. -1.0 +/- 0.3 cmH(2)O.l(-1).s, P = 0.18). Positive-pressure inflation of the lungs can significantly enhance deep inspiration-induced bronchodilation in patients with asthma.

Expression of smooth muscle and extracellular matrix proteins in relation to airway function in asthma.

BACKGROUND: Smooth muscle content is increased within the airway wall in patients with asthma and is likely to play a role in airway hyperresponsiveness. However, smooth muscle cells express several contractile and structural proteins, and each of these proteins may influence airway function distinctly. OBJECTIVE: We examined the expression of contractile and structural proteins of smooth muscle cells, as well as extracellular matrix proteins, in bronchial biopsies of patients with asthma, and related these to lung function, airway hyperresponsiveness, and responses to deep inspiration. METHODS: Thirteen patients with asthma (mild persistent, atopic, nonsmoking) participated in this cross-sectional study. FEV(1)% predicted, PC(20) methacholine, and resistance of the respiratory system by the forced oscillation technique during tidal breathing and deep breath were measured. Within 1 week, a bronchoscopy was performed to obtain 6 bronchial biopsies that were immunohistochemically stained for alpha-SM-actin, desmin, myosin light chain kinase (MLCK), myosin, calponin, vimentin, elastin, type III collagen, and fibronectin. The level of expression was determined by automated densitometry. RESULTS: PC(20) methacholine was inversely related to the expression of alpha-smooth muscle actin (r = -0.62), desmin (r = -0.56), and elastin (r = -0.78). In addition, FEV(1)% predicted was positively related and deep inspiration-induced bronchodilation inversely related to desmin (r = -0.60), MLCK (r = -0.60), and calponin (r = -0.54) expression. CONCLUSION: Airway hyperresponsiveness, FEV(1)% predicted, and airway responses to deep inspiration are associated with selective expression of airway smooth muscle proteins and components of the extracellular matrix.

A syringe simulation of biological controls for quality assessment of prospective lung volume measurements.

BACKGROUND: At present a syringe is being used for calibration of lung function devices, but biological controls are used to detect prospectively the variability and reproducibility of lung volumes measured by spirometers. Laboratory personnel is often used as biological control and therefore the cost for these measurements is substantial and may be reduced by replacement of a syringe procedure to increase the capacity of the laboratory to measure more patients. OBJECTIVES: To develop a mechanical syringe procedure for identification of instrument problems. METHODS: A commercial 3-liter precision syringe is used to simulate breathing maneuvers (inspiratory vital capacity, functional residual capacity, residual volume and total lung capacity) on a spirometer. Three healthy males representing biological controls performed spirometry, maximum expiratory flow volume and helium dilution forced residual capacity at bimonthly intervals for 3 years. Confidence intervals and interval widths are calculated for each parameter. Levene's test for equality of variances was used to test for significance between standard deviations. RESULTS: The interval width of inspiratory vital capacity, functional residual capacity, total lung capacity and residual volume of repeated measurements obtained from the syringe was significantly narrower than those of biological controls. In addition, almost all standard deviations from lung volumes obtained from the syringe were smaller and significantly different from those of the biological control. CONCLUSION: Our syringe procedure may replace biological controls for detection of variability of lung volumes. This will result in cost reduction and improve quality assessment of lung function devices.

An electronic nose in the discrimination of patients with asthma and controls.

BACKGROUND: Exhaled breath contains thousands of volatile organic compounds (VOCs) that could serve as biomarkers of lung disease. Electronic noses can distinguish VOC mixtures by pattern recognition. OBJECTIVE: We hypothesized that an electronic nose can discriminate exhaled air of patients with asthma from healthy controls, and between patients with different disease severities. METHODS: Ten young patients with mild asthma (25.1 +/- 5.9 years; FEV(1), 99.9 +/- 7.7% predicted), 10 young controls (26.8 +/- 6.4 years; FEV(1), 101.9 +/- 10.3), 10 older patients with severe asthma (49.5 +/- 12.0 years; FEV(1), 62.3 +/- 23.6), and 10 older controls (57.3 +/- 7.1 years; FEV(1), 108.3 +/- 14.7) joined a cross-sectional study with duplicate sampling of exhaled breath with an interval of 2 to 5 minutes. Subjects inspired VOC-filtered air by tidal breathing for 5 minutes, and a single expiratory vital capacity was collected into a Tedlar bag that was sampled by electronic nose (Cyranose 320) within 10 minutes. Smellprints were analyzed by linear discriminant analysis on principal component reduction. Cross-validation values (CVVs) were calculated. RESULTS: Smellprints of patients with mild asthma were fully separated from young controls (CVV, 100%; Mahalanobis distance [M-distance], 5.32), and patients with severe asthma could be distinguished from old controls (CVV, 90%; M-distance, 2.77). Patients with mild and severe asthma could be less well discriminated (CVV, 65%; M-distance, 1.23), whereas the 2 control groups were indistinguishable (CVV, 50%; M-distance, 1.56). The duplicate samples replicated these results. CONCLUSION: An electronic nose can discriminate exhaled breath of patients with asthma from controls but is less accurate in distinguishing asthma severities. CLINICAL IMPLICATION: These findings warrant validation of electronic noses in diagnosing newly presented patients with asthma.

Bronchial inflammation and airway responses to deep inspiration in asthma and chronic obstructive pulmonary disease.

RATIONALE: Deep inspirations provide physiologic protection against airway narrowing in healthy subjects, which is impaired in asthma and chronic obstructive pulmonary disease (COPD). Airway inflammation has been suggested to alter airway mechanics during deep inspiration. OBJECTIVES: We tested the hypothesis that the number of bronchial inflammatory cells is related to deep inspiration-induced bronchodilation in asthma and COPD. METHODS: In a cross-sectional study, three modified methacholine challenges were performed in 13 patients with mild, persistent asthma, 12 patients with mild to moderate COPD, and 12 healthy control subjects. MEASUREMENTS AND MAIN RESULTS: After a 20-minute period of deep inspiration avoidance, inhalation of methacholine was followed by either one or five deep inspirations, or preceded by five deep inspirations. The response to deep inspiration was measured by forced oscillation technique. Inflammatory cells were counted within the lamina propria and airway smooth muscle area in bronchial biopsies of patients with asthma and COPD. The reduction in expiratory resistance by one and five deep inspirations was significantly less in asthma (mean change+/-SD: -0.5+/-0.8 and -0.9+/-1.0 cm H2O/L/s, respectively) and COPD (+0.2+/-1.1 and +0.4+/-1.0 cm H2O/L/s, respectively) as compared with healthy subjects (-1.5+/-1.3 and -2.0+/-1.2 cm H2O/L/s, respectively; p=0.05 and p=0.001, respectively). In asthma, this was related to an increase in mast cell numbers within the airway smooth muscle area (r=0.73; p=0.03), and in CD4+ lymphocytes in the lamina propria (r=0.61; p=0.04). CONCLUSIONS: Inflammation in the airway smooth muscle bundles and submucosa of bronchial biopsies is positively associated with impaired airway mechanics during deep inspiration in asthma, but not in COPD. Clinical trial registered with www.clinicaltrials.gov (NCT OO279136).

Automatic negative evaluation of suffocation sensations in individuals with suffocation fear.

The current study tested whether "suffocation sensations" (respiratory loads) are automatically evaluated in a negative way by people fearing these sensations. It was found that, after having been primed with a slight respiratory load, participants with high suffocation fear (n=15) reacted more quickly to suffocation words and more slowly to positive words than participants with low suffocation fear (n=21). However, the effect was present only in participants who had noticed the primes. The findings are relevant to the cognitive model of panic disorder because automatic negative appraisal of sensations may play a role in initiating a panic attack.

Real-time MR imaging of aortic flow: influence of breathing on left ventricular stroke volume in chronic obstructive pulmonary disease.

PURPOSE: To assess real-time changes of left ventricular stroke volume (SV) in relation to the breathing pattern in healthy subjects and in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: Real-time magnetic resonance (MR) imaging flow measurements were performed in the ascending aorta of 10 healthy volunteers and nine patients with severe COPD. Breathing maneuvers were registered with an abdominal pressure belt, which was synchronized to the electrocardiographic signal and the flow measurement. Healthy subjects performed normal breathing, deep breathing, and the Valsalva maneuver. Patients with COPD performed spontaneous breathing. Paired two-tailed Student t tests were used in healthy volunteers to assess significant SV differences between normal breathing and deep breathing or the Valsalva maneuver. The results of measurements in the patients with COPD were compared with the results during normal breathing in healthy subjects with the unpaired two-tailed Student t test. RESULTS: In healthy subjects, SV decreased during inspiration and increased during expiration (r2 = 0.78, P <.05). When compared with the SV during normal breathing, mean SV did not change during deep breathing but declined during the Valsalva maneuver (P <.05). The difference between minimal and maximal SVs (ie, SV range) increased because of deep breathing or the Valsalva maneuver (P <.05). In normal and deep breathing, velocity of SV elevation and velocity of SV decrease were equal (which resulted in a ratio of 1), whereas during the Valsalva maneuver, this value increased (P <.05). Spontaneous breathing in COPD resulted in SV changes (P <.05) similar to those observed in healthy subjects who performed the Valsalva maneuver. CONCLUSION: Real-time MR imaging of aortic flow reveals physiologic flow alterations, which are dependent on variations in the breathing pattern.