Noninvasive autonomic nervous system assessment in respiratory disorders and sport sciences applications

La presente tesis está centrada en el análisis no invasivo de señales cardíacas y respiratorias, con el objetivo de evaluar la actividad del sistema nervioso autónomo (ANS) en diferentes escenarios, tanto clínicos como no clínicos. El documento está estructurado en tres partes principales. La primera parte consiste en una introducción a los aspectos fisiológicos y metodológicos que serán cubiertos en el resto de la tesis. En la segunda parte, se analiza la variabilidad del ritmo cardiaco (HRV) en el contexto de enfermedades respiratorias, concretamente asma (tanto en niños como en adultos) y apnea del sueño. En la tercera parte, se estudian algunas aplicaciones novedosas del análisis de señales cardiorespiratorias en el campo de las ciencias del deporte. La primera parte está compuesta por los capítulos 1 y 2. El capítulo 1 consiste en una extensa introducción al funcionamiento del sistema nervioso autónomo y las características de las bioseñales analizadas a lo largo de la tesis. Por otro lado, se aborda la patofisiología del asma y la apnea del sueño, su relación con el funcionamiento del ANS y las estrategias de diagnóstico y tratamiento de lasmismas. El capítulo concluye con una introducción a la fisiología del ejercicio, así como al interés en la estimación del volumen tidal y del umbral anaeróbico en el campo de las ciencias del deporte.En cuanto al capítulo 2, se presenta un marco de trabajo para el análisis contextualizado de la HRV. Después de una descripción de las técnicas de evaluación y acondicionamiento de la señal de HRV, el capítulo se centra en el efecto de los latidos ectópicos, la arritmia sinusal respiratoria y la frecuencia respiratoria en el análisis de la HRV.Además, se discute el uso de un índice para la evaluación de la distribución de la potencia en los espectros de HRV, así como diferentes medidas de acoplo cardiorespiratorio.La segunda parte está compuesta por los capítulos 3, 4 y 5, todos ellos relacionados con el análisis de la HRV en enfermedades respiratorias. Mientras que los capítulos 3 y 4 están centrados en asma infantil y en adultos respectivamente, el capítulo 5 aborda la apnea del sueño. El asma es una enfermedad respiratoria crónica que aparece habitualmente acompañada por una inflamación de las vías respiratorias. Aunque afecta a personas detodas las edades, normalmente se inicia en edades tempranas, y ha llegado a constituir una de las enfermedades crónicasmás comunes durante la infancia. Sin embargo, todavía no existe un método adecuado para el diagnóstico de asma en niños pequeños. Por otro lado, el rol fundamental que desempeña el sistema nervioso parasimpático en el control del tono bronco-motor y la bronco-dilatación sugiere que la rama parasimpática del ANS podría estar implicada en la patogénesis del asma. De estemodo, en el capítulo 3 se evalúa el ANS mediante el análisis de la HRV en dos bases de datos diferentes, compuestas por niños en edad pre-escolar clasificados en función de su riesgo de desarrollar asma, o de su condición asmática actual. Los resultados del análisis revelaron un balance simpáticovagal reducido y una componente espectral de alta frecuencia más picuda en aquellos niños con un mayor riesgo de desarrollar asma. Además, la actividad parasimpática y el acoplo cardiorespiratorio se redujeron en un grupo de niños con bajo riesgo de asma al finalizar un tratamiento para bronquitis obstructiva, mientras que estos permanecieron inalterados en aquellos niños con una peor prógnosis.A diferencia de los niños pequeños, en el caso de adultos el diagnóstico de asma se realiza a través de una rutina clínica bien definida. Sin embargo, la estratificación de los pacientes en función de su grado de control de los síntomas se basa generalmente en el uso de cuestionarios auto-aplicados, que pueden tener un carácter subjetivo. Por otro lado, la evaluación de la severidad del asma requiere de una visita hospitalaria y de incómodas pruebas, que no pueden aplicarse de una forma continua en el tiempo. De este modo, en el capítulo 4 se estudia el valor de la evaluación del ANS para la estratificación de adultos asmáticos. Para ello, se emplearon diferentes características extraídas de la HRV y la respiración, junto con varios parámetros clínicos, para entrenar un conjunto de algoritmos de clasificación. La inclusión de características relacionadas con el ANS para clasificar los sujetos atendiendo a la severidad del asma derivó en resultados similares al caso de utilizar únicamente parámetros clínicos, superando el desempeño de estos últimos en algunos casos. Por lo tanto, la evaluación del ANS podría representar un potencial complemento para la mejora de la monitorización de sujetos asmáticos.En el capítulo 5, se analiza la HRV en sujetos que padecen el síndrome de apnea del sueño (SAS) y comorbididades cardíacas asociadas. El SAS se ha relacionado con un incremento de 5 veces en el riesgo de desarrollar enfermedades cardiovasculares (CVD), que podría aumentar hasta 11 veces si no se trata convenientemente. Por otro lado, una HRV alterada se ha relacionado independientemente con el SAS y con numerosos factores de riesgo para el desarrollo de CVD. De este modo, este capítulo se centra en evaluar si una actividad autónoma desbalanceada podría estar relacionada con el desarrollo de CVD en pacientes de SAS. Los resultados del análisis revelaron una dominancia simpática reducida en aquellos sujetos que padecían SAS y CVD, en comparación con aquellos sin CVD. Además, un análisis retrospectivo en una base de datos de sujetos con SAS que desarollarán CVD en el futuro también reveló una actividad simpática reducida, sugiriendo que un ANS desbalanceado podría constituir un factor de riesgo adicional para el desarrollo de CVD en pacientes de SAS.La tercera parte está formada por los capítulos 6 y 7, y está centrada en diferentes aplicaciones del análisis de señales cardiorespiratorias en el campo de las ciencias del deporte. El capítulo 6 aborda la estimación del volumen tidal (TV) a partir del electrocardiograma (ECG). A pesar de que una correcta monitorización de la actividad respiratoria es de gran interés en ciertas enfermedades respiratorias y en ciencias del deporte, la mayor parte de la actividad investigadora se ha centrado en la estimación de la frecuencia respiratoria, con sólo unos pocos estudios centrados en el TV, la mayoría de los cuales se basan en técnicas no relacionadas con el ECG. En este capítulo se propone un marco de trabajo para la estimación del TV en reposo y durante una prueba de esfuerzo en tapiz rodante utilizando únicamente parámetros derivados del ECG. Errores de estimación del 14% en la mayoría de los casos y del 6% en algunos sugieren que el TV puede estimarse a partir del ECG, incluso en condiciones no estacionarias.Por último, en el capítulo 7 se propone una metodología novedosa para la estimación del umbral anaeróbico (AT) a partir del análisis de las dinámicas de repolarización ventricular. El AT representa la frontera a partir de la cual el sistema cardiovascular limita la actividad física de resistencia, y aunque fue inicialmente concebido para la evaluación de la capacidad física de pacientes con CVD, también resulta de gran interés en el campo de las ciencias del deporte, permitiendo diseñar mejores rutinas de entrenamiento o para prevenir el sobre-entrenamiento. Sin embargo, la evaluación del AT requiere de técnicas invasivas o de dispositivos incómodos. En este capítulo, el AT fue estimado a partir del análisis de las variaciones de las dinámicas de repolarización ventricular durante una prueba de esfuerzo en cicloergómetro. Errores de estimación de 25 W, correspondientesa 1 minuto en este estudio, en un 63% de los sujetos (y menores que 50 W en un 74% de ellos) sugieren que el AT puede estimarse de manera no invasiva, utilizando únicamente registros de ECG.<br /

Therapeutic alternatives with CPAP in obstructive sleep apnea

Obstructive Sleep Apnea (OSA), characterized by airflow cessation (apnea) or reduction (hypopnea) due to repeated pharyngeal obstructions during sleep, causes frequent disruption of sleep and hypoxic events. The condition is linked to many adverse health related consequences, such as neurocognitive and cardiovascular disorders, and metabolic syndrome. OSA is a chronic condition requiring long-term treatment, so treatment using continuous positive airway pressure (CPAP) has become the gold standard in cases of moderate or severe OSA. However, its effectiveness is influenced by patients’ adherence. Surgery for OSA or treatment with oral appliances can be successful in selected patients, but for the majority, lifestyle changes such as exercise and dietary control may prove useful. However, exercise training remains under-utilized by many clinicians as an alternative treatment for OSA. Other interventions such as oral appliance (OA), upper way stimulation, and oropharyngeal exercises are used in OSA. Because the benefit of all these techniques is heterogeneous, the major challenge is to associate specific OSA therapies with the maximum efficacy and the best patient compliance

Assessment of Body Composition and Heart Rate Variability in Bronchial Asthma

Background: Previous&nbsp; studies were focused mainly either on autonomic modulation using heart rate variability (HRV) or body composition in the bronchial asthma patients, but our study has correlated&nbsp; both&nbsp; HRV and body composition&nbsp; indices in&nbsp; asthmatic patients. Aim &amp; Objective:To evaluate the possible association of HRV and body composition parameters&nbsp; with&nbsp; main&nbsp; spirometric&nbsp; indices&nbsp; in newly diagnosed asthmatic&nbsp; patients &amp; to compare these findings with healthy subjects. Methods: Thirty&nbsp;&nbsp; asthmatic&nbsp; patients (study group ) and 30 apparently healthy subjects (controls) in age group of 20-55 years of both genders&nbsp; were included.&nbsp; BMI, waist- hip ratio (WHR)&nbsp;&nbsp; and&nbsp; body fat % were measured. Time&nbsp; and&nbsp; frequency&nbsp; domain&nbsp; parameters of HRV&nbsp;&nbsp; were recorded to determine sympathetic and parasympathetic autonomic modulations. Forced vital Capacity (FVC),&nbsp; Forced&nbsp; expiratory&nbsp; volume&nbsp; at&nbsp; 1st second (FEV1) &amp; FEV1/FVC ratio parameters were recorded.Results: HF ms2 &amp; HF n.u were significantly (P&lt;0.001) higher and LF n.u &amp; LF-HF &nbsp;ratio&nbsp; were significantly (P&lt;0.001)&nbsp; lower in asthmatics as compared to control. WHR was found to be significantly higher in study group as compared to control (P&lt;0.001). We found a negative correlation of LF n.u &amp; LF- HF ratio &amp; positive&nbsp; correlation&nbsp; of&nbsp; HF n.u with FEV1(L), FEV1/FVC %&nbsp; &amp;&nbsp; WHR which&nbsp; was&nbsp; not found statistically significant. Conclusion: In our study we observed altered autonomic activity with parasympathetic dominance as HF component was higher in asthmatic patients. We also found a significant association between WHR and asthma. Key words : &nbsp;Bronchial asthma,&nbsp; body composition,&nbsp; heart rate variability

Therapeutic alternatives with CPAP in obstructive sleep apnea

Obstructive Sleep Apnea (OSA), characterized by airflow cessation (apnea) or reduction (hypopnea) due to repeated pharyngeal obstructions during sleep, causes frequent disruption of sleep and hypoxic events. The condition is linked to many adverse health related consequences, such as neurocognitive and cardiovascular disorders, and metabolic syndrome. OSA is a chronic condition requiring long-term treatment, so treatment using continuous positive airway pressure (CPAP) has become the gold standard in cases of moderate or severe OSA. However, its effectiveness is influenced by patients’ adherence. Surgery for OSA or treatment with oral appliances can be successful in selected patients, but for the majority, lifestyle changes such as exercise and dietary control may prove useful. However, exercise training remains under-utilized by many clinicians as an alternative treatment for OSA. Other interventions such as oral appliance (OA), upper way stimulation, and oropharyngeal exercises are used in OSA. Because the benefit of all these techniques is heterogeneous, the major challenge is to associate specific OSA therapies with the maximum efficacy and the best patient compliance

Measurement and analysis of breath sounds

Existing breath sound measurement systems and possible new methods have been critically investigated. The frequency response of each part of the measurement system has been studied. Emphasis has been placed on frequency response of acoustic sensors; especially, a method to study a diaphragm type air-coupler in contact use has been proposed. Two new methods of breath sounds measurement have been studied: laser Doppler vibrometer and mobile phones. It has been shown that these two methods can find applications in breath sounds measurement, however there are some restrictions. A reliable automatic wheeze detection algorithm based on auditory modelling has been developed. That is the human’s auditory system is modelled as a bank of band pass filters, in which the bandwidths are frequency dependent. Wheezes are treated as signals additive to normal breath sounds (masker). Thus wheeze is detectable when it is above the masking threshold. This new algorithm has been validated using simulated and real data. It is superior to previous algorithms, being more reliable to detect wheezes and less prone to mistakes. Simulation of cardiorespiratory sounds and wheeze audibility tests have been developed. Simulated breath sounds can be used as a training tool, as well as an evaluation method. These simulations have shown that, under certain circumstance, there are wheezes but they are inaudible. It is postulated that this could also happen in real measurements. It has been shown that simulated sounds with predefined characteristics can be used as an objective method to evaluate automatic algorithms. Finally, the efficiency and necessity of heart sounds reduction procedures has been investigated. Based on wavelet decomposition and selective synthesis, heart sounds can be reduced with a cost of unnatural breath sounds. Heart sound reduction is shown not to be necessary if a time-frequency representation is used, as heart sounds have a fixed pattern in the time-frequency plane

Inaugural Review Prize 2023: The exercise hyperpnoea dilemma:A 21st‐century perspective

During mild or moderate exercise, alveolar ventilation increases in direct proportion to metabolic rate, regulating arterial CO2 pressure near resting levels. Mechanisms giving rise to the hyperpnoea of exercise are unsettled despite over a century of investigation. In the past three decades, neuroscience has advanced tremendously, raising optimism that the ‘exercise hyperpnoea dilemma’ can finally be solved. In this review, new perspectives are offered in the hope of stimulating original ideas based on modern neuroscience methods and current understanding. We first describe the ventilatory control system and the challenge exercise places upon blood‐gas regulation. We highlight relevant system properties, including feedforward, feedback and adaptive (i.e., plasticity) control of breathing. We then elaborate a seldom explored hypothesis that the exercise ventilatory response continuously adapts (learns and relearns) throughout life and ponder if the memory ‘engram’ encoding the feedforward exercise ventilatory stimulus could reside within the cerebellum. Our hypotheses are based on accumulating evidence supporting the cerebellum's role in motor learning and the numerous direct and indirect projections from deep cerebellar nuclei to brainstem respiratory neurons. We propose that cerebellar learning may be obligatory for the accurate and adjustable exercise hyperpnoea capable of tracking changes in life conditions/experiences, and that learning arises from specific cerebellar microcircuits that can be interrogated using powerful techniques such as optogenetics and chemogenetics. Although this review is speculative, we consider it essential to reframe our perspective if we are to solve the till‐now intractable exercise hyperpnoea dilemma

Long-term effects of CPAP therapy on patients with sleep-disordered breathing

The population of patients suffering from sleep-disordered breathing (SDB), especiallyobstructive sleep apnoea (OSA) is rising. OSA is often treated with continuous positive airway pressure (CPAP), but data on the long-term effects are scarce. SDB is an umbrella term for different types of SDB, that may have a similar nocturnal breathingdisorder, while the underlying mechanisms are different as well as the risks that comefrom having an untreated condition. In the future, treatment will be more individualised, and CPAP therapy might not be the first or the best choice for all patients. Thus, more information on the long-term effects of CPAP therapy is needed. In order to study the lifestyle, weight changes, and leptin and Insulin-like GrowthFactor 1 (IGF-1) concentrations during long-term CPAP therapy, patients who were referred to the Pulmonary ward of the Turku University Hospital for suspected sleep apnoea were enrolled in the study (n=223). Patients were given an array of questionnaires on sleep duration and quality, sleepiness, depressive symptoms and anxiety, cravings for different food categories, and exercise habits. All had a cardiorespiratory polygraphy (PG), and their blood was drawn following an overnight fast. After three years of follow-up, the patients were divided into CPAP users (n= 76) and non-users (n= 73), and all measurements except the sleep study, were repeated. The use of medication for comorbidities was evaluated for women referred to Paimio Hospital between 1994-1998 for suspected sleep apnoea (n= 601).The medication data were derived from the National Reimbursement registration three years before, and three years after CPAP initiation or the sleep study. Women were divided into CPAP users (n=66) and the control group (n= 122). The SDB type was also considered in the analysis. In our study, long-term CPAP therapy alleviated SDB symptoms, depressive symptoms, and anxiety efficiently. However, it did not influence lifestyle or exercise habits, and the patients did not lose weight. Increase in weight was associated with a good adherence to CPAP. In women, leptin concentrations increased, especially if they used CPAP. IGF-1 concentrations did not change. Medication use for comorbidities continued to increase regardless of CPAP therapy and CPAP users already had more comorbidities before the CPAP therapy initiation. However, the increase in medicine use did not differ between the CPAP users and non-users. The type of SDB also did not influence medicine use. In conclusion, patients with SDB should have sufficient life-style counselling aswell as CPAP therapy. CPAP therapy does not automatically decrease medication use and thus the cost. Earlier diagnosis and treatment of SDB before end-organ manifestations might instead reduce health care costs. The different profile for female SDB patients should also be noted and remembered.Unenaikaista hengityshäiriötä sairastavien määrä on kasvussa, ja erityisesti obstruktiivista uniapneaa sairastavia potilaita on vuosi vuodelta enemmän. Uniapneaa hoidetaan usein ylipainehengityslaitteella (continuous positive airway pressure, CPAP). Unenaikainen hengityshäiriö on sateenvarjotermi, jonka altalöytyy eri alatyyppejä, joita yhdistävät unenaikaiset hengityskatkokset, mutta niiden syntymekanismit ja riskiprofiili vaihtelevat. Tulevaisuudessa siirryttäneenkin yksilöllisempään hoitoon, jolloin CPAP ei ole ensisijainen hoitomuoto kaikille. Tämän vuoksi lisätieto CPAP-hoidon pitkäaikaisvaikutuksista on erityisen tärkeää. Tutkiaksemme elintapoja, painon muutosta sekä leptiinin ja insuliinikaltaisen kasvutekijä 1:n (IGF-1) pitoisuuksia pitkäaikaisen CPAP-hoidon aikana, Turun yliopistollisen keskussairaalan keuhkoklinikalle uniapneaepäilyn vuoksi lähetetyille223 potilaalle annettiin kyselylomakkeita, joissa kysyttiin unen pituudesta ja laadusta,uneliaisuudesta, masennus-tai ahdistusoireista, erilaisten ruokien mieliteoista sekä liikuntatottumuksista. Lisäksi heille tehtiin yöpolygrafia ja otettiin paastoverinäyte. Potilaat jaettiin kolmen vuoden seuranta-ajan jälkeen CPAP-käyttäjiin (n=76) ja ei-käyttäjiin (n=73) ja heille tehtiin yöpolygrafiaa lukuun ottamatta samat tutkimukset. Lääkkeiden käyttöä tutkittiin Paimion sairaalaan v. 1994-1998 uniapneaepäilyn vuoksiunipatjatutkimukseen tulleiden naisten avulla (n=601). Lääkekäyttötiedot Kelalta pyydettiin kolme vuotta ennen ja kolme vuotta laitehoidon aloituksen tai rekiste¬röintipäivän jälkeen. Naiset jaettiin joko CPAP-käyttäjiin (n=66) tai verrokkeihin (n=122). Myös unenaikaisen hengityshäiriön tyyppi otettiin huomioon. Tutkimuksessamme pitkäaikainen CPAP-hoito lievitti tehokkaasti unenaikaisen hengityshäiriön oireita sekä masennus- ja ahdistuneisuusoireita. Hoidolla ei ollut vaikutusta potilaiden elintapoihin, eivätkä potilaat laihtuneet. Painon nousu oli yhteydessä tehokkaaseen CPAP-laitteen käyttöön. Naisilla leptiinipitoisuudet nousivat hoidon aikana, erityisesti jos he käyttivät CPAP-laitetta. Insuliininkaltaisen kasvutekijä 1:n-pitoisuudet eivät muuttuneet. Liitännäissairauksien lääkekäyttö jatkoi nousuaan CPAP-hoidosta huolimatta, ja CPAP:n käyttäjillä oli jo alkuvaiheessa enemmän sairauksia kuin verrokeilla. Lääkekäytön lisääntyminen ei eronnut CPAP-hoitoa käyttävillä ja ei-käyttäjillä. Unenaikaisen hengityshäiriön tyypillä ei ollut vaikutusta lääkekäyttöön. Tulostemme valossa ehdotamme, että uniapneaa sairastaville tulisi CPAP-hoidon lisäksi tarjota tehokasta elintapavalmennusta. CPAP-hoito ei automaattisesti vähennä lääkekulutusta. Varhaisempi uniapnean diagnosointi ja hoito saattaisi estääliitännäissairauksien kehittymistä ja säästää terveydenhuollon kuluja. Lisäksi naisten erilainen taudinkuva tulisi muistaa

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