POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of Innovation and Technology Health (EIT Health) project

Allergic rhinitis (AR) is impacted by allergens and air pollution but interactions between air pollution, sleep and allergic diseases are insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and Rhinitis) is a project of the European Institute of Innovation and Technology (EIT Health). It will use a freely-existing application for AR monitoring that has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000 users, TLR8). The Allergy Diary will be combined with a new tool allowing queries on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as existing longitudinal and geolocalized pollution data. Machine learning will be used to assess the relationship between air pollution, sleep and AR comparing polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be confirmed in 2019 and extended by the individual prospective assessment of pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a demonstrator of sleep disorder that can be modulated in terms of symptoms and severity by air pollution and AR. The geographic information system GIS will map the results. Consequences on quality of life (EQ-5D), asthma, school, work and sleep will be monitored and disseminated towards the population. The impacts of POLLAR will be (1) to propose novel care pathways integrating pollution, sleep and patients’ literacy, (2) to study sleep consequences of pollution and its impact on frequent chronic diseases, (3) to improve work productivity, (4) to propose the basis for a sentinel network at the EU level for pollution and allergy, (5) to assess the societal implications of the interaction. MASK paper N°32.     

Does clinical outcome of birch pollen immunotherapy relate to induction of blocking antibodies preventing IgE from allergen binding? A pilot study monitoring responses during first year of AIT

Background

The clinical benefit of allergen-specific immunotherapy (AIT) involves induction of blocking antibodies. It is not clear if these antibodies function via steric hindrance alone or a combination of levels, avidities, and epitope specificities, and clinical outcome cannot be predicted. We aim to in-depth characterize serum antibody profiles during birch pollen AIT, investigate therapy-induced antibodies for their capacity to block IgE binding to Bet v 1 and correlate data with clinical outcomes.

Methods

Immune responses of five birch pollen allergic patients were monitored during the first year of AIT by nasal provocation tests (NPTs), ImmunoCAP, immunoblots, direct and avidity enzyme-linked immunosorbent assays, mediator release assays, facilitated antigen binding (FAB) assays, and inhibition mediator release assays.

Results

There was no correlation between NPT results and therapy-induced changes in levels (IgE, IgG, IgA, IgM), avidities, or mediator release potency of Bet v 1-specific antibodies. In FAB assays, blocking antibodies initiated upon AIT were shown to prevent formation of Bet v 1-IgE complexes of an indicator serum pool and significantly correlated with clinical readout. Inhibition mediator release assays using patient-specific IgE for passive sensitization revealed therapy-induced blocking capacities with very good correlation to NPT results. Notably, this assay was the only one to detect a non-responder during treatment in this pilot study.

Conclusions

Clinical outcome of AIT depends on induction of blocking antibodies able to prevent the patient’s own IgE from allergen binding. Monitoring of clinical efficacy seems to be best achieved using the inhibition mediator release assay, as development of relevant blocking antibodies can be verified in a patient-tailored manner.

     

Alpha 1 antitrypsin distribution in an allergic asthmatic population sensitized to house dust mites

Background and objective

Severe alpha1 antitrypsin deficiency has been clearly associated with pulmonary emphysema, but its relationship with bronchial asthma remains controversial. Some deficient alpha 1 antitrypsin (AAT) genotypes seem to be associated with asthma development. The objective of this study was to analyze the distribution of AAT genotypes in asthmatic patients allergic to house dust mites (HDM), and to asses a possible association between these genotypes and severe asthma.

Methods

A cross-sectional cohort study of 648 patients with HDM allergic asthma was carried out. Demographic, clinical and analytical variables were collected. PI*S and PI*Z AAT deficient alleles of the SERPINA1 gene were assayed by real-time PCR.

Results

Asthma was intermittent in 253 patients and persistent in 395 patients (246 mild, 101 moderate and 48 severe). One hundred and forty-five asthmatic patients (22.4%) with at least one mutated allele (S or Z) were identified. No association between the different genotypes and asthma severity was found. No significant differences in all clinical and functional tests, as well as nasal eosinophils, IgA and IgE serum levels were observed. Peripheral eosinophils were significantly lower in patients with the PI*MS genotype (p?=?0.0228). Neither association between deficient AAT genotypes or serum ATT deficiency (AATD) and development of severe asthma, or correlation between ATT levels and FEV1 was observed.

Conclusion

In conclusion, the distribution of AAT genotypes in HDM allergic asthmatic patients did not differ from those found in Spanish population. Neither severe ATTD or deficient AAT genotypes appear to confer different clinical expression of asthma.

     

Improvement in diagnostic delays over time in patients with hereditary angioedema: findings from the Icatibant Outcome Survey

The objective of this analysis was to evaluate the change over time in age at first symptoms, age at diagnosis, and delay in diagnosis using data from the Icatibant Outcome Survey (IOS). Patients with a diagnosis of C1-INH-HAE who were born before the year 1990 and who were diagnosed before they reached 25 years of age were included in the analysis. Both age at diagnosis and delay in diagnosis of C1-INH-HAE appear to decline with later decade of birth, despite wide variation across the countries assessed, suggesting that improved disease awareness causes increased rates of earlier diagnosis over time. Our findings demonstrate that some patients are still experiencing long delays to diagnosis, indicating an ongoing need for improved disease awareness.     

A qualitative study exploring parents’ experiences with epinephrine use for their child’s anaphylactic reaction

Background

Children with life threatening food allergies live with the constant threat of a fatal reaction, and caregivers must always be prepared to treat with an epinephrine auto-injector (EAI). This interpretive phenomenological study explored parents’ perceptions and lived experiences with prescribed EAI use for their child.

Methods

The purposive sample included ten parents of five children under 12 years of age, diagnosed with a food allergy and prescribed with an EAI who recently experienced anaphylaxis. Data sources included digitally-recorded semi-structured interviews and a reflexive journal.

Results

Eight main themes emerged: perception of anaphylaxis, life challenges, isolation, anxiety, hesitation, guilt, influence of health care professionals, and lessons learned. Parents uniformly described multiple life challenges and feelings of isolation, anxiety and hesitation during a reaction that lead to subsequent guilt.

Conclusions

Handling reactions correctly provided parents with confidence to treat subsequent reactions. Witnessing the effects of an EAI and receiving positive feedback from health care providers further strengthened their confidence to quickly and competently intervene in future reactions.

     

Regenerative peripheral nerve interfaces for real-time,proportional control of a Neuroprosthetic hand

Introduction

Regenerative peripheral nerve interfaces (RPNIs) are biological constructs which amplify neural signals and have shown long-term stability in rat models. Real-time control of a neuroprosthesis in rat models has not yet been demonstrated. The purpose of this study was to: a) design and validate a system for translating electromyography (EMG) signals from an RPNI in a rat model into real-time control of a neuroprosthetic hand, and; b) use the system to demonstrate RPNI proportional neuroprosthesis control.

Methods

Animals were randomly assigned to three experimental groups: (1) Control; (2) Denervated, and; (3) RPNI. In the RPNI group, the extensor digitorum longus (EDL) muscle was dissected free, denervated, transferred to the lateral thigh and neurotized with the residual end of the transected common peroneal nerve. Rats received tactile stimuli to the hind-limb via monofilaments, and electrodes were used to record EMG. Signals were filtered, rectified and integrated using a moving sample window. Processed EMG signals (iEMG) from RPNIs were validated against Control and Denervated group outputs.

Results

Voluntary reflexive rat movements produced signaling that activated the prosthesis in both the Control and RPNI groups, but produced no activation in the Denervated group. Signal-to-Noise ratio between hind-limb movement and resting iEMG was 3.55 for Controls and 3.81 for RPNIs. Both Control and RPNI groups exhibited a logarithmic iEMG increase with increased monofilament pressure, allowing graded prosthetic hand speed control (R²?=?0.758 and R²?=?0.802, respectively).

Conclusion

EMG signals were successfully acquired from RPNIs and translated into real-time neuroprosthetic control. Signal contamination from muscles adjacent to the RPNI was minimal. RPNI constructs provided reliable proportional prosthetic hand control.

     

Experimental comparisons of passive and powered ankle-foot orthoses in individuals with limb reconstruction

Background

Ankle-foot orthoses (AFO) are commonly prescribed to provide functional assistance for patients with lower limb injuries or weakness. Their passive mechanical elements can provide some energy return to improve walking ability, but cannot restore plantar flexor push-off. Powered AFOs provide an assistive torque about the ankle to address the limitations of passive devices, but current designs have yet to be implemented on a large scale clinically. Purpose: To compare passive AFOs to a new untethered, powered AFO design in a clinical population with lower limb reconstruction.

Methods

A crossover study design, conducted on three individuals with lower limb reconstruction, compared gait mechanics at a standardized speed (based on leg length) in 4 AFO conditions: 1. None (shoes only), 2. Blue Rocker (BR, Allard, USA), 3. Intrepid Dynamic Exoskeletal Orthosis (IDEO), and 4. PowerFoot Orthosis (PFO BionX Medical Technologies, Inc.). The PFO was a custom, battery-powered device whose damping and power were capable to being tuned to meet patient needs. Subjects performed biomechanical gait analysis and metabolic testing at slow, moderate and fast speeds. Dependent variables included total limb power (calculated using a unified deformable segment model), mechanical work, mechanical efficiency, ankle motion, net metabolic cost across three speeds, and performance measures were calculated. Effect sizes (d) were calculated and d?>?0.80 denoted a large effect.

Results

Net positive work (d > 1.17) and efficiency (d > 1.43) were greatest in the PFO. There were large effects for between limb differences in positive work for all conditions except the PFO (d?=?0.75). The PFO normalized efficiency between the affected and unaffected limbs (d?=?0.50), whereas efficiency was less on the affected limb for all other conditions (d > 1.69). Metabolic rate was not consistently lowest in any one AFO condition across speeds. Despite some positive results of the PFO, patient preferred their daily use AFO (2 IDEO, 1 BR). All participants indicated that mass and size were concerns with using the PFO.

Conclusions

A novel PFO resulted in more biomimetic mechanical work and efficiency than commercially-available and custom passive AFO models. Although the powered AFO provided some biomechanical benefits, further improvements are warranted to improve patient satisfaction.

     

Machine learning algorithms for activity recognition in ambulant children and adolescents with cerebral palsy

Background

Cerebral palsy (CP) is the most common physical disability among children (2.5 to 3.6 cases per 1000 live births). Inadequate physical activity (PA) is a major problem effecting the health and well-being of children with CP. Practical, yet accurate measures of PA are needed to evaluate the effectiveness of surgical and therapy-based interventions to increase PA. Accelerometer-based motion sensors have become the standard for objectively measuring PA in children and adolescents; however, current methods for estimating physical activity intensity in children with CP are associated with significant error and may dramatically underestimate HPA in children with more severe mobility limitations. Machine learning (ML) models that first classify the PA type and then predict PA intensity or energy expenditure using activity specific regression equations may be more accurate than standalone regression models. However, the feasibility and validity of ML methods has not been explored in youth with CP. Therefore, the purpose of this study was to develop and test ML models for the automatic identification of PA type in ambulant children with CP.

Methods

Twenty two children and adolescents (mean age: 12.8?±?2.9 y) with CP classified at GMFCS Levels I to III completed 7 activity trials while wearing an ActiGraph GT3X+ accelerometer on the hip and wrist. Trials were categorised as sedentary (SED), standing utilitarian movements (SUM), comfortable walking (CW), and brisk walking (BW). Random forest (RF), support vector machine (SVM), and binary decision tree (BDT) classifiers were trained with features extracted from the vector magnitude (VM) of the raw acceleration signal using 10?s non-overlapping windows. Performance was evaluated using leave-one-subject out cross validation.

Results

SVM (82.0–89.0%) and RF (82.6–88.8%) provided significantly better classification accuracy than BDT (76.1–86.2%). Hip (82.7–85.5%) and wrist (76.1–82.6%) classifiers exhibited comparable prediction accuracy, while the combined hip and wrist (86.2–89.0%) classifiers achieved the best overall performance. For all classifiers, recognition accuracy was excellent for SED (94.1–97.9%), good to excellent for SUM (74.0–96.6%) and brisk walking (71.5–86.0%), and modest for comfortable walking (47.6–70.4%). When comfortable and brisk walking were combined into a single walking class, recognition accuracy ranged from 90.3 to 96.5%.

Conclusions

ML methods provided acceptable classification accuracy for detection of a range of activities commonly performed by ambulatory children with CP. The resultant models can help clinicians more effectively monitor bouts of brisk walking in the community. The results indicate that 2-step models that first classify PA type and then predict energy expenditure using activity specific regression equations are worthy of exploration in this patient group.

     

Stochastic resonance stimulation improves balance in children with cerebral palsy: a case control study

Background

Stochastic Resonance (SR) Stimulation has been used to enhance balance in populations with sensory deficits by improving the detection and transmission of afferent information. Despite the potential promise of SR in improving postural control, its use in individuals with cerebral palsy (CP) is novel. The objective of this study was to investigate the immediate effects of electrical SR stimulation when applied in the ankle muscles and ligaments on postural stability in children with CP and their typically developing (TD) peers.

Methods

Ten children with spastic diplegia (GMFCS level I- III) and ten age-matched TD children participated in this study. For each participant the SR sensory threshold was determined. Then, five different SR intensity levels (no stimulation, 25, 50, 75, and 90% of sensory threshold) were used to identify the optimal SR intensity for each subject. The optimal SR and no stimulation condition were tested while children stood on top of 2 force plates with their eyes open and closed. To assess balance, the center of pressure velocity (COPV) in anteroposterior (A/P) and medial-lateral (M/L) direction, 95% COP confidence ellipse area (COPA), and A/P and M/L root mean square (RMS) measures were computed and compared.

Results

For the CP group, SR significantly decreased COPV in A/P direction, and COPA measures compared to the no stimulation condition for the eyes open condition. In the eyes closed condition, SR significantly decreased COPV only in M/L direction. Children with CP demonstrated greater reduction in all the COP measures but the RMS in M/L direction during the eyes open condition compared to their TD peers. The only significant difference between groups in the eyes closed condition was in the COPV in M/L direction.

Conclusions

SR electrical stimulation may be an effective stimulation approach for decreasing postural sway and has the potential to be used as a therapeutic tool to improve balance. Applying subject-specific SR stimulation intensities is recommended to maximize balance improvements. Overall, balance rehabilitation interventions in CP might be more effective if sensory facilitation methods, like SR, are utilized by the clinicians.

Trial registration

ClinicalTrials.gov identifier NCT02456376; 28 May 2015 (Retrospectively registered); https://clinicaltrials.gov/ct2/show/NCT02456376.

     

Validating attentive locomotion training using interactive treadmill: an fNIRS study

Background

Existing treadmill-based locomotion training, which has been used for gait function recovery, still has limitations, such as less attentive training. Interactive treadmills (ITMs) were developed to overcome these limitations, but it has not yet been verified that ITMs can make the user pay closer attention to walk training.

Methods

An experimental comparison between ITMs and conventional treadmills was conducted by measuring the level of the user’s attention using functional near-infrared spectroscopy (fNIRS). To consider the effect of task complexity on the subject’s attention, we provided two (slow and fast) speed conditions for walking on both treadmills.

Results

Both the cortical activity images and oxygenated hemoglobin (oxyHb) changes showed that the level of attention to walking induced by the ITM was significantly higher than that induced by the conventional treadmill. We found that the walking speed on the ITM also affected the level of attention.

Conclusion

ITM-based locomotion training would be a promising solution to the limitations of existing treadmill-based locomotion training currently used to improve gait function recovery.

Trial registration

DGIST-HR-150309-03-02. Registered 01 March 2015.