WEARCON: wearable home monitoring in children with asthma reveals a strong association with hospital based assessment of asthma control.

BACKGROUND: Asthma is one of the most common chronic diseases in childhood. Regular follow-up of physiological parameters in the home setting, in relation to asthma symptoms, can provide complementary quantitative insights into the dynamics of the asthma status. Despite considerable interest in asthma home-monitoring in children, there is a paucity of scientific evidence, especially on multi-parameter monitoring approaches. Therefore, the aim of this study is to investigate whether asthma control can be accurately assessed in the home situation by combining parameters from respiratory physiology sensors. METHODS: Sixty asthmatic and thirty non-asthmatic children were enrolled in the observational WEARCON-study. Asthma control was assessed according to GINA guidelines by the paediatrician. All children were also evaluated during a 2-week home-monitoring period with wearable devices; a physical activity tracker, a handheld spirometer, smart inhalers, and an ambulatory electrocardiography device to monitor heart and respiratory rate. Multiple logistic regression analysis was used to determine which diagnostic measures were associated with asthma control. RESULTS: 24 of the 27 uncontrolled asthmatic children and 29 of the 32 controlled asthmatic children could be accurately identified with this model. The final model showed that a larger variation in pre-exercise lung function (OR = 1.34 95%-CI 1.07-1.68), an earlier wake-up-time (OR = 1.05 95%-CI 1.01-1.10), more reliever use (OR = 1.11 95%-CI 1.03-1.19) and a longer respiratory rate recovery time (OR = 1.12 95%-CI 1.05-1.20) were significant contributors to the probability of having uncontrolled asthma. CONCLUSIONS: Home-monitoring of physiological parameters correlates with paediatrician assessed asthma control. The constructed multivariate model identifies 88.9% of all uncontrolled asthmatic children, indicating a high potential for monitoring of asthma control. This may allow healthcare professionals to assess asthma control at home. TRIAL REGISTRATION: Netherlands Trail Register, NL6087 . Registered 14 February 2017.

What the pulmonary specialist should know about the new inhalation therapies.

A collaboration of multidisciplinary experts on the delivery of pharmaceutical aerosols was facilitated by the European Respiratory Society (ERS) and the International Society for Aerosols in Medicine (ISAM), in order to draw up a consensus statement with clear, up-to-date recommendations that enable the pulmonary physician to choose the type of aerosol delivery device that is most suitable for their patient. The focus of the consensus statement is the patient-use aspect of the aerosol delivery devices that are currently available. The subject was divided into different topics, which were in turn assigned to at least two experts. The authors searched the literature according to their own strategies, with no central literature review being performed. To achieve consensus, draft reports and recommendations were reviewed and voted on by the entire panel. Specific recommendations for use of the devices can be found throughout the statement. Healthcare providers should ensure that their patients can and will use these devices correctly. This requires that the clinician: is aware of the devices that are currently available to deliver the prescribed drugs; knows the various techniques that are appropriate for each device; is able to evaluate the patient's inhalation technique to be sure they are using the devices properly; and ensures that the inhalation method is appropriate for each patient.

Volatile organic breath components and exercise induced bronchoconstriction in asthmatic children.

INTRODUCTION: Asthma is one of the most common chronic diseases in childhood and is generally characterized by exercise induced bronchoconstriction (EIB). Assessing EIB is time consuming and expensive as it requires a fully equipped pulmonary function laboratory. Analysis of volatile organic compounds (VOCs) in breath is a novel technique for examining biomarkers which may associate with asthma features. The aim of this pilot study was to identify potential markers in the relationship between EIB and VOCs. METHODS: Children between four and 14 years old were asked to provide a breath sample prior to undergoing an exercise challenge test to assess for EIB. RESULTS: Breath samples were collected and analyzed in 46 asthmatic children, 21 with EIB and 25 without EIB (NO-EIB). Molecular features (MFs) were not significantly different between EIB and NO-EIB controls. 29 of the 46 children were corticosteroid naïve, 10 with EIB and 13 without. In the corticosteroid naïve group EIB was associated with increased MF23 and MF14 in the lower breath sample (p-value < 0.05). CONCLUSION: This pilot study shows that EIB was related to an increased MF14 and MF23 in corticosteroid naïve children. The tentative identities of these compounds are octanal and dodecane/tetradecane respectively. These candidate biomarkers have a potential to enable non-invasive diagnosis of EIB in steroid-naïve children. Trial registration This study is registered in the Netherlands trial register (trial no. NL6087) at 14 February 2017.

The Mozart study: a relation between dynamic hyperinflation and physical activity in patients with chronic obstructive pulmonary disease?

BACKGROUND: Many patients with chronic obstructive pulmonary disease (COPD) experience dyspnoea during exercise, resulting in a reduction of physical activity (PA). Dynamic hyperinflation (DH) is seen as a major cause of dyspnoea in COPD. OBJECTIVE: The objective of the current study was to investigate the relationship between DH, in terms of the amount of DH and the development and recovery rate of DH in patients with COPD, and PA. METHODS: Thirty-five patients with stable COPD were included from an outpatient clinic (14 GOLD II and 21 GOLD III, median age 65). PA was assessed using an accelerometer. Subjects underwent metronome-paced tachypnoea (MPT) to induce DH. To quantify the amount of DH during MPT, a decrease in inspiratory capacity (IC) or a change in IC as percentage of total lung capacity was used. RESULTS: No significant correlations were found between the parameters describing DH and PA. Secondary correlation analyses showed a negative correlation between static hyperinflation (SH) and PA (r = -0·39; P = 0·02). The pattern of breathing during MPT and the test itself showed high interpatient variability. CONCLUSIONS: The absence of a significant correlation between DH and PA is contrary to previous studies. SH did show a correlation with PA. The variety in results and the technical difficulties in execution of the measurements ask for a new, more reliable, method to detect DH and investigate its relation with PA in patients with COPD.

Multi-centre prospective study on diagnosing subtypes of lung cancer by exhaled-breath analysis.

OBJECTIVES: Lung cancer is a leading cause of mortality. Exhaled-breath analysis of volatile organic compounds (VOC's) might detect lung cancer early in the course of the disease, which may improve outcomes. Subtyping lung cancers could be helpful in further clinical decisions. MATERIALS AND METHODS: In a prospective, multi-centre study, using 10 electronic nose devices, 144 subjects diagnosed with NSCLC and 146 healthy subjects, including subjects considered negative for NSCLC after investigation, breathed into the Aeonose™ (The eNose Company, Zutphen, Netherlands). Also, analyses into subtypes of NSCLC, such as adenocarcinoma (AC) and squamous cell carcinoma (SCC), and analyses of patients with small cell lung cancer (SCLC) were performed. RESULTS: Choosing a cut-off point to predominantly rule out cancer resulted for NSCLC in a sensitivity of 94.4%, a specificity of 32.9%, a positive predictive value of 58.1%, a negative predictive value (NPV) of 85.7%, and an area under the curve (AUC) of 0.76. For AC sensitivity, PPV, NPV, and AUC were 81.5%, 56.4%, 79.5%, and 0.74, respectively, while for SCC these numbers were 80.8%, 45.7%, 93.0%, and 0.77, respectively. SCLC could be ruled out with a sensitivity of 88.9% and an NPV of 96.8% with an AUC of 0.86. CONCLUSION: Electronic nose technology with the Aeonose™ can play an important role in rapidly excluding lung cancer due to the high negative predictive value for various, but not all types of lung cancer. Patients showing positive breath tests should still be subjected to further diagnostic testing.

A newly developed tool for intra-tracheal temperature and humidity assessment in laryngectomized individuals: the Airway Climate Explorer (ACE).

The aim of this study is to develop a postlaryngectomy airway climate explorer (ACE) for assessment of intratracheal temperature and humidity and of influence of heat and moisture exchangers (HMEs). Engineering goals were within-device condensation prevention and fast response time characteristics. The ACE consists of a small diameter, heated air-sampling catheter connected to a heated sensor house, containing a humidity sensor. Air is sucked through the catheter by a controlled-flow pump. Validation was performed in a climate chamber using a calibrated reference sensor and in a two-flow system. Additionally, the analyser was tested in vivo. Over the clinically relevant range of humidity values (5-42 mg H2O/l air) the sensor output highly correlates with the reference sensor readings (R2 > 0.99). The 1-1/e response times are all <0.5 s. A first in vivo pilot measurement was successful. The newly developed, verified, fast-responding ACE is suitable for postlaryngectomy airway climate assessment.

Aerosol deposition in the upper airways of a child.

In a small child, normally only a small amount of inhaled aerosol particles reaches the lungs because the majority deposits in the upper airways. In this study, the upper airways of a 9- month-old child, based on computed tomography (CT) data, are modeled to serve as input for a computational fluid dynamics package (CFX). Verification of the validity of aerosol deposition calculations by this package is accomplished by evaluating two test cases, which also can be solved analytically. The numerically found sedimentation fraction in a horizontally placed straight pipe shows deviations from the exact solution for small particle sizes (less than 3 micron) due to small velocities generated by the use of an unstructured mesh. Although these velocities are small compared to the mainstream velocity, they are comparable with the terminal settling velocity of such a particle. Also the test case for inertial impaction in a bend pipe demonstrated the same problem. With this in mind, the aerosol deposition of 3.7-micron particles in the upper airway model of the child (SAINT-model) was calculated. Results were compared with experimentally found results in the literature. For small tidal volumes and flow rates, the computational results matched the experimentally measured results. However, large deviations were found for higher flow rates and small particle sizes. Most probably the incompletely modeled entrance at the nose and inertial effects due to turbulence might be responsible.

Reversibility of pulmonary function after inhaling salbutamol in different doses and body postures in asthmatic children.

RATIONALE: Pulmonary medication is often delivered in the form of medical aerosols designed for inhalation. Recently, breath actuated inhalers (BAI's) gained popularity as they can be used without spacers. A major drawback of BAI's is the impaction in the upper airway. Stretching the upper airway by a forward leaning body posture with the neck extended ("sniffing position") during inhalation may reduce upper airway impaction and improve pulmonary deposition. Aim of this study was to investigate the reversibility of lung function with different doses salbutamol inhaled with a BAI in the forward leaning posture compared to the standard posture in asthmatic children. METHODS: 22 clinically stable asthmatic children, 5-14 years old, performed four reversibility measurements. Children inhaled 200 µg or 400 µg salbutamol with a BAI in the standard or in the forward leaning posture with the neck extended in a randomized single-blinded cross-over design. RESULTS: Reversibility of lung function after inhaling salbutamol in the forward leaning posture was not significantly different compared to inhalation in the standard posture. Mean FEV1 reversibility was significantly greater after inhaling 400 µg salbutamol compared to 200 µg salbutamol in the standard posture (9.4% ± 9.5% versus 4.5% ± 7.5%, difference 4.9% (95CI 0.9; 9.0%); p = 0.021). CONCLUSION: In clinically stable asthmatic children, inhalation of salbutamol with a BAI in a forward leaning posture does not increase reversibility of lung function. Inhalation of 400 µg compared to 200 µg salbutamol with a BAI does improve reversibility.

Reversibility after inhaling salbutamol in different body postures in asthmatic children: a pilot study.

RATIONALE: Pulmonary medication is mostly delivered in the form of medical aerosols to minimize systemic side effects. A major drawback of inhaled medication is that the majority of inhaled particles impacts in the oropharynx at the sharp bend of the airway. Stretching the airway by a forward leaning body posture with the neck extended ("sniffing position") may improve pulmonary deposition and clinical effects. METHODS: 41 asthmatic children who were planned for standard reversibility testing at the pulmonary function lab, alternately inhaled 200 µgr salbutamol with an Autohaler(®) in the standard or in the forward leaning body posture. Forced Expiratory Volume in 1 s (FEV1), Forced Vital Capacity (FVC), Peak Expiratory Flow (PEF), Mean Expiratory Flow at 25% of vital capacity (MEF25) and Mean Expiratory Flow at 75% of vital capacity (MEF75) were analysed. RESULTS: The children in the forward leaning body posture group showed a significantly higher mean FEV1 reversibility than the control group after inhalation of 200 µgr salbutamol (10.2% versus 4.1%, p = 0.019). Additionally, mean MEF75 was significantly more reversible in the forward leaning body posture group versus the standard body posture group (32.2% resp. 8.9%, p = 0.013). CONCLUSION: This pilot study showed a higher reversibility of FEV1 and MEF75 after inhaling salbutamol in a forward leaning body posture compared to the standard body posture in asthmatic children. This suggests that pulmonary effects of salbutamol can be improved by inhaling in a forward leaning body posture with the neck extended. This effect is possibly due to a higher pulmonary deposition of salbutamol and should be confirmed in a randomized controlled trial.

Integration of electronic nose technology with spirometry: validation of a new approach for exhaled breath analysis.

New 'omics'-technologies have the potential to better define airway disease in terms of pathophysiological and clinical phenotyping. The integration of electronic nose (eNose) technology with existing diagnostic tests, such as routine spirometry, can bring this technology to 'point-of-care'. We aimed to determine and optimize the technical performance and diagnostic accuracy of exhaled breath analysis linked to routine spirometry. Exhaled breath was collected in triplicate in healthy subjects by an eNose (SpiroNose) based on five identical metal oxide semiconductor sensor arrays (three arrays monitoring exhaled breath and two reference arrays monitoring ambient air) at the rear end of a pneumotachograph. First, the influence of flow, volume, humidity, temperature, environment, etc, was assessed. Secondly, a two-centre case-control study was performed using diagnostic and monitoring visits in day-to-day clinical care in patients with a (differential) diagnosis of asthma, chronic obstructive pulmonary disease (COPD) or lung cancer. Breathprint analysis involved signal processing, environment correction based on alveolar gradients and statistics based on principal component (PC) analysis, followed by discriminant analysis (Matlab2014/SPSS20). Expiratory flow showed a significant linear correlation with raw sensor deflections (R(2) = 0.84) in 60 healthy subjects (age 43 ± 11 years). No correlation was found between sensor readings and exhaled volume, humidity and temperature. Exhaled data after environment correction were highly reproducible for each sensor array (Cohen's Kappa 0.81-0.94). Thirty-seven asthmatics (41 ± 14.2 years), 31 COPD patients (66 ± 8.4 years), 31 lung cancer patients (63 ± 10.8 years) and 45 healthy controls (41 ± 12.5 years) entered the cross-sectional study. SpiroNose could adequately distinguish between controls, asthma, COPD and lung cancer patients with cross-validation values ranging between 78-88%. We have developed a standardized way to integrate eNose technology with spirometry. Signal processing techniques and environmental background correction ensured that the multiple sensor arrays within the SpiroNose provided repeatable and interchangeable results. SpiroNose discriminated controls and patients with asthma, COPD and lung cancer with promising accuracy, paving the route towards point-of-care exhaled breath diagnostics.

Protective effect of a low single dose inhaled steroid against exercise induced bronchoconstriction.

OBJECTIVE: Daily use of inhaled corticosteroids (ICS) reduces exercise induced bronchoconstriction (EIB) in asthmatic children. A high single dose of ICS also provided acute protection against EIB. Objective of this study is to investigate whether a low single dose of ICS offers protection against EIB in asthmatic children. METHODS: 31 Mild asthmatic children not currently treated with inhaled corticosteroids, 5-16 years, with EIB (fall in FEV0.5/1 ≥ 13%) were included in a prospective intervention study. They performed two ECT's within 2 weeks. Four hours before the second test children inhaled 200 µg beclomethasone-dipropionate (BDP) with a breath-actuated inhaler (BAI). RESULTS: The median fall in FEV0.5/1 after 200 µg BDP was significantly reduced from 30.9% at baseline to 16.0% (P < 0.001). Twenty children (64.5%) showed a good response to 200 µg BDP (≥ 50% decrease in fall of FEV0.5/1), while 8 children showed a moderate response (25-50%), and three children showed no response at all (< 25%). CONCLUSION: A low single dose ICS offers acute protection against EIB in the majority of asthmatic children not currently treated with inhaled corticosteroids.

Pneumothorax in a preterm infant monitored by electrical impedance tomography: a case report.

Electrical impedance tomography (EIT) is a noninvasive bedside tool for monitoring regional changes in ventilation. We report, for the first time, the EIT images of a ventilated preterm infant with a unilateral pneumothorax, showing a loss of regional ventilation in the affected lung during both high-frequency oscillation and spontaneous ventilation.

Effects of a single dose inhaled corticosteroid on the dynamics of airway obstruction after exercise.

RATIONALE: Exercise-induced bronchoconstriction (EIB) is defined as a transient narrowing of the airways induced by exercise. Repetitive measurements of spirometric parameters, such as FEV(1) and expiratory flows, and forced oscillation technique (FOT) measurements can be used to analyze the dynamics of EIB. A single high dose of fluticasone propionate (FP) protects against EIB. The aim of the study was to analyze the effect of FP on the dynamics of exercise-induced airway narrowing as measured with FOT and spirometry. METHODS: Twelve children performed an exercise challenge on 2 separate days, 4 hr after inhalation of 1 mg FP (pressurized metered dose inhaler) or a placebo. Before and after the exercise flow-volume loops as well as the FOT (frequency range: 4-32 Hz) were measured. RESULTS: The FEV(1) , and FEF(50) fell significantly after exercise within groups; the peak fall in FEV(1) after FP was significantly smaller than after placebo (respectively, 19.3 ± 14.6% and 29.2 ± 14.8%, P = 0.03, 95% CI: 0.9-18.8%). The fall in FEV(1) and FEF(50) peaked 3 min after exercise and showed a subsequent partial recovery. The fall in the FEV(1) /FVC ratio showed a later peak fall (12 min after exercise). The resistance increased while the reactance decreased significantly after exercise. FP significantly decreased the maximal increase in Rrs(6) when compared to the placebo (respectively 176.5 ± 59.1% and 201.0 ± 63.8%, P = 0.05, 95% CI: 0.5-48.7%). The maximal decrease in Xrs(6) was not significantly affected by FP (P = 0.06). CONCLUSION: Repetitive spirometric and FOT measurements after exercise show a rapid narrowing and steady recovery of the patency of the conducting airways, and indicate a delayed and prolonged recovery of the smaller airways. A single high dose of inhaled FP seems to employ its effect mainly in the conducting airways.

The physiological rationale of heat and moisture exchangers in post-laryngectomy pulmonary rehabilitation: a review.

Total laryngectomy results in a permanent disconnection of the upper and lower airways and inevitably leads to chronic pulmonary complaints like frequent involuntary coughing, increased sputum production and repeated daily forced expectoration to clean the airway. Heat and moisture exchangers (HMEs), applied in an attempt to compensate for the lost functions of the upper respiratory tract, have been found to diminish these symptoms and improve the quality of life significantly. An HME has three physical properties that might be responsible for these improvements. First, its heat and moisture exchanging capacity improves intra-airway preservation of heat and water. Since the condensation and evaporation of moisture are accompanied by the release and uptake of thermal energy, these parameters are inseparable. Secondly, the HME's resistance may reduce dynamic airway compression, thereby improving ventilation. Thirdly, to some extent, an HME might filter out particles, thereby cleaning inspiratory breathing air. This article summarizes our present knowledge of changes in respiratory physiology after total laryngectomy and the influence of the HME by reviewing the physiological impact of these three physical properties separately for in vitro and in vivo data.