Impedance Pneumography for the Nocturnal Assessment of Lower Airway Obstruction

Tidal breathing analysis is a lung function technique suggested for infants and children who are unable to cooperate with forced spirometry. This technique aims to quantify lower airway obstruction from average changes in the shape or the breath-to-breath variations of the tidal breathing flow-volume loop (TBFV) profiles. If tidal airflow is recorded with a mouth pneumotachograph (PNT), tidal breathing analysis finds the same limitations as other alternatives to spirometry. These are typically the need for sedation and the assessment of lung function only for sort times at the hospital. Recent improvements in impedance pneumography (IP) enable for the first time the continuous non-invasive monitoring of respiratory airflow overnight. This can improve the analysis of tidal breathing by capturing circadian and nocturnal worsening in lower airway obstruction. However, due to the lack of previous methods recording nocturnal airflow, little is known about how the interaction of sleep physiology and lower airway obstruction is reflected in the shape and variability of tidal breathing. This thesis reviews the literature regarding shape and variability analysis of tidal breathing during lower airway obstruction, sleep, or maturation. The thesis also extends this knowledge by presenting four original publications. The first publication describes a technical improvement in the IP method. The other three study the nocturnal TBFV’s shape in wheezing infants and children, and the nocturnal TBFV’s variability in healthy children. Both the literature and the results agree that for the TBFVs’ shape, increasing lower air- way obstruction advances the peak of expired flow and turns the middle part from convex to concave. However, these changes occur at a different degree of obstruction for differ- ent subjects depending on the compensation strategy that they have chosen. In infants, changes putatively occur at a higher degree of obstruction because most of the expiration is controlled by the respiratory musculature. During rapid eye movement (REM) sleep, changes putatively occur at a lower degree of obstruction because muscle atony limits the compensation strategies. For the variability of TBFVs, increasing lower airway obstruction decreases the variability in the early part of expiration in the long term (the whole night). However, the short-term variability is dominated by the stage-dependent variations in the respiratory drive. The thesis concludes that, at the present, tidal breathing analysis can estimate lower airway obstruction but cannot quantify its degree with accuracy. However, nocturnal IP recordings are easy to conduct and can serve as a first-line diagnosis or for the monitoring of disease progression. Nonetheless, future improvements in signal processing and the understanding of the tidal airflow signal can easily increase the accuracy and find new applications

Multichannel bioimpedance measurement

This thesis is a research about the possibility of measure bioimpedance simultaneously in different body locations. It first rises a theoretical study facing the problem as a classic multichannel communication system with share channel, analysing the software and hardware problems involved for all the possibilities. The more suitable configuration chosen is based on frequency multiplexation, it consists of injecting isolated sine waves with different frequencies for each channel and uses a bandpass filter to get only the required one. About the signal processing the best option found is to record the signal using undersampling techniques and implements the filter digitally. Moreover a three channel test device has been made following the calculations for a eight channels one, in order to test the theoretical research and to find possible practical limitations. Finally this test device has been used for a concrete purpose, the breathing measuring in three points on the thorax

Sources of variability in expiratory flow profiles during sleep in healthy young children

Standard lung function tests are not feasible in young children, but recent studies show that the variability of expiratory tidal breathing flow-volume (TBFV) curves during sleep is a potential indirect marker of lower airway obstruction. However, the neurophysiological sources of the TBFV variability in normal subjects has not been established. We investigated sleep stages and body position changes as potential sources for the TBFV curve variability. Simultaneous impedance pneumography (IP), polysomnography (PSG) and video recordings were done in 20 children aged 1.4-6.9 years without significant respiratory disorders during sleep. The early part of expiratory TBFV curves are less variable between cycles of REM than NREM sleep. However, within individual sleep cycles, TBFV curves during N3 are the least variable. The differences in TBFV curve shapes between sleep stages are the main source of overnight variability in TBFV curves and the changes in body position have a lesser impact.Peer reviewe

Glyph-based visualization of health trajectories

Whenever a diagnosis is given, a procedure is performed, or a drug is prescribed, it leads to an entry into an electronic health record (EHR) system. Previously, this data was difficult to utilize because of rules regarding confidentiality, but new security approaches and pseudonymization have enabled us to work with this data. Health-related data is voluminous and complex, and it can be difficult to abstract a meaningful overview. One of the complexities is its longitudinality. Often medical research is cross-sectional - we often take a point in time for analysis, when instead, it might be more beneficial to see the trajectory that led to the point in time. We are currently developing a trajectory visualization tool for longitudinal electronic health data. It is a web-based tool that interfaces with the OHDSI data infrastructure and visualizes the cohorts and concept sets (groups of medical codes) defined via the OHDSI Atlas GUI. Currently, our tool is in user testing and it will be deployed to a wider user group during the spring. The user feedback has been positive. Users find the tool especially useful in understanding and debugging their OHDSI Atlas cohort definitions.acceptedVersionPeer reviewe

Expiratory variability index is associated with asthma risk, wheeze and lung function in infants with recurrent respiratory symptoms

Non peer reviewe

FinnGen provides genetic insights from a well-phenotyped isolated population

Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.publishedVersionPeer reviewe

Impedance Pneumography for the Nocturnal Assessment of Lower Airway Obstruction

Tidal breathing analysis is a lung function technique suggested for infants and children who are unable to cooperate with forced spirometry. This technique aims to quantify lower airway obstruction from average changes in the shape or the breath-to-breath variations of the tidal breathing flow-volume loop (TBFV) profiles. If tidal airflow is recorded with a mouth pneumotachograph (PNT), tidal breathing analysis finds the same limitations as other alternatives to spirometry. These are typically the need for sedation and the assessment of lung function only for sort times at the hospital. Recent improvements in impedance pneumography (IP) enable for the first time the continuous non-invasive monitoring of respiratory airflow overnight. This can improve the analysis of tidal breathing by capturing circadian and nocturnal worsening in lower airway obstruction. However, due to the lack of previous methods recording nocturnal airflow, little is known about how the interaction of sleep physiology and lower airway obstruction is reflected in the shape and variability of tidal breathing. This thesis reviews the literature regarding shape and variability analysis of tidal breathing during lower airway obstruction, sleep, or maturation. The thesis also extends this knowledge by presenting four original publications. The first publication describes a technical improvement in the IP method. The other three study the nocturnal TBFV’s shape in wheezing infants and children, and the nocturnal TBFV’s variability in healthy children. Both the literature and the results agree that for the TBFVs’ shape, increasing lower air- way obstruction advances the peak of expired flow and turns the middle part from convex to concave. However, these changes occur at a different degree of obstruction for differ- ent subjects depending on the compensation strategy that they have chosen. In infants, changes putatively occur at a higher degree of obstruction because most of the expiration is controlled by the respiratory musculature. During rapid eye movement (REM) sleep, changes putatively occur at a lower degree of obstruction because muscle atony limits the compensation strategies. For the variability of TBFVs, increasing lower airway obstruction decreases the variability in the early part of expiration in the long term (the whole night). However, the short-term variability is dominated by the stage-dependent variations in the respiratory drive. The thesis concludes that, at the present, tidal breathing analysis can estimate lower airway obstruction but cannot quantify its degree with accuracy. However, nocturnal IP recordings are easy to conduct and can serve as a first-line diagnosis or for the monitoring of disease progression. Nonetheless, future improvements in signal processing and the understanding of the tidal airflow signal can easily increase the accuracy and find new applications

Multichannel bioimpedance measurement

This thesis is a research about the possibility of measure bioimpedance simultaneously in different body locations. It first rises a theoretical study facing the problem as a classic multichannel communication system with share channel, analysing the software and hardware problems involved for all the possibilities. The more suitable configuration chosen is based on frequency multiplexation, it consists of injecting isolated sine waves with different frequencies for each channel and uses a bandpass filter to get only the required one. About the signal processing the best option found is to record the signal using undersampling techniques and implements the filter digitally. Moreover a three channel test device has been made following the calculations for a eight channels one, in order to test the theoretical research and to find possible practical limitations. Finally this test device has been used for a concrete purpose, the breathing measuring in three points on the thorax