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

Multichannel analysis of normal and continuous adventitious respiratory sounds for the assessment of pulmonary function in respiratory diseases

Premi extraordinari doctorat UPC curs 2015-2016, àmbit d’Enginyeria IndustrialRespiratory sounds (RS) are produced by turbulent airflows through the airways and are inhomogeneously transmitted through different media to the chest surface, where they can be recorded in a non-invasive way. Due to their mechanical nature and airflow dependence, RS are affected by respiratory diseases that alter the mechanical properties of the respiratory system. Therefore, RS provide useful clinical information about the respiratory system structure and functioning. Recent advances in sensors and signal processing techniques have made RS analysis a more objective and sensitive tool for measuring pulmonary function. However, RS analysis is still rarely used in clinical practice. Lack of a standard methodology for recording and processing RS has led to several different approaches to RS analysis, with some methodological issues that could limit the potential of RS analysis in clinical practice (i.e., measurements with a low number of sensors, no controlled airflows, constant airflows, or forced expiratory manoeuvres, the lack of a co-analysis of different types of RS, or the use of inaccurate techniques for processing RS signals). In this thesis, we propose a novel integrated approach to RS analysis that includes a multichannel recording of RS using a maximum of five microphones placed over the trachea and the chest surface, which allows RS to be analysed at the most commonly reported lung regions, without requiring a large number of sensors. Our approach also includes a progressive respiratory manoeuvres with variable airflow, which allows RS to be analysed depending on airflow. Dual RS analyses of both normal RS and continuous adventitious sounds (CAS) are also proposed. Normal RS are analysed through the RS intensity–airflow curves, whereas CAS are analysed through a customised Hilbert spectrum (HS), adapted to RS signal characteristics. The proposed HS represents a step forward in the analysis of CAS. Using HS allows CAS to be fully characterised with regard to duration, mean frequency, and intensity. Further, the high temporal and frequency resolutions, and the high concentrations of energy of this improved version of HS, allow CAS to be more accurately characterised with our HS than by using spectrogram, which has been the most widely used technique for CAS analysis. Our approach to RS analysis was put into clinical practice by launching two studies in the Pulmonary Function Testing Laboratory of the Germans Trias i Pujol University Hospital for assessing pulmonary function in patients with unilateral phrenic paralysis (UPP), and bronchodilator response (BDR) in patients with asthma. RS and airflow signals were recorded in 10 patients with UPP, 50 patients with asthma, and 20 healthy participants. The analysis of RS intensity–airflow curves proved to be a successful method to detect UPP, since we found significant differences between these curves at the posterior base of the lungs in all patients whereas no differences were found in the healthy participants. To the best of our knowledge, this is the first study that uses a quantitative analysis of RS for assessing UPP. Regarding asthma, we found appreciable changes in the RS intensity–airflow curves and CAS features after bronchodilation in patients with negative BDR in spirometry. Therefore, we suggest that the combined analysis of RS intensity–airflow curves and CAS features—including number, duration, mean frequency, and intensity—seems to be a promising technique for assessing BDR and improving the stratification of BDR levels, particularly among patients with negative BDR in spirometry. The novel approach to RS analysis developed in this thesis provides a sensitive tool to obtain objective and complementary information about pulmonary function in a simple and non-invasive way. Together with spirometry, this approach to RS analysis could have a direct clinical application for improving the assessment of pulmonary function in patients with respiratory diseases.Los sonidos respiratorios (SR) se generan con el paso del flujo de aire a través de las vías respiratorias y se transmiten de forma no homogénea hasta la superficie torácica. Dada su naturaleza mecánica, los SR se ven afectados en gran medida por enfermedades que alteran las propiedades mecánicas del sistema respiratorio. Por lo tanto, los SR proporcionan información clínica relevante sobre la estructura y el funcionamiento del sistema respiratorio. La falta de una metodología estándar para el registro y procesado de los SR ha dado lugar a la aparición de diferentes estrategias de análisis de SR con ciertas limitaciones metodológicas que podrían haber restringido el potencial y el uso de esta técnica en la práctica clínica (medidas con pocos sensores, flujos no controlados o constantes y/o maniobras forzadas, análisis no combinado de distintos tipos de SR o uso de técnicas poco precisas para el procesado de los SR). En esta tesis proponemos un método innovador e integrado de análisis de SR que incluye el registro multicanal de SR mediante un máximo de cinco micrófonos colocados sobre la tráquea yla superficie torácica, los cuales permiten analizar los SR en las principales regiones pulmonares sin utilizar un número elevado de sensores . Nuestro método también incluye una maniobra respiratoria progresiva con flujo variable que permite analizar los SR en función del flujo respiratorio. También proponemos el análisis combinado de los SR normales y los sonidos adventicios continuos (SAC), mediante las curvas intensidad-flujo y un espectro de Hilbert (EH) adaptado a las características de los SR, respectivamente. El EH propuesto representa un avance importante en el análisis de los SAC, pues permite su completa caracterización en términos de duración, frecuencia media e intensidad. Además, la alta resolución temporal y frecuencial y la alta concentración de energía de esta versión mejorada del EH permiten caracterizar los SAC de forma más precisa que utilizando el espectrograma, el cual ha sido la técnica más utilizada para el análisis de SAC en estudios previos. Nuestro método de análisis de SR se trasladó a la práctica clínica a través de dos estudios que se iniciaron en el laboratorio de pruebas funcionales del hospital Germans Trias i Pujol, para la evaluación de la función pulmonar en pacientes con parálisis frénica unilateral (PFU) y la respuesta broncodilatadora (RBD) en pacientes con asma. Las señales de SR y flujo respiratorio se registraron en 10 pacientes con PFU, 50 pacientes con asma y 20 controles sanos. El análisis de las curvas intensidad-flujo resultó ser un método apropiado para detectar la PFU , pues encontramos diferencias significativas entre las curvas intensidad-flujo de las bases posteriores de los pulmones en todos los pacientes , mientras que en los controles sanos no encontramos diferencias significativas. Hasta donde sabemos, este es el primer estudio que utiliza el análisis cuantitativo de los SR para evaluar la PFU. En cuanto al asma, encontramos cambios relevantes en las curvas intensidad-flujo yen las características de los SAC tras la broncodilatación en pacientes con RBD negativa en la espirometría. Por lo tanto, sugerimos que el análisis combinado de las curvas intensidad-flujo y las características de los SAC, incluyendo número, duración, frecuencia media e intensidad, es una técnica prometedora para la evaluación de la RBD y la mejora en la estratificación de los distintos niveles de RBD, especialmente en pacientes con RBD negativa en la espirometría. El método innovador de análisis de SR que se propone en esta tesis proporciona una nueva herramienta con una alta sensibilidad para obtener información objetiva y complementaria sobre la función pulmonar de una forma sencilla y no invasiva. Junto con la espirometría, este método puede tener una aplicación clínica directa en la mejora de la evaluación de la función pulmonar en pacientes con enfermedades respiratoriasAward-winningPostprint (published version

Defining the role of mast cells in guinea pig models of asthma

Asthma is a common respiratory disease characterized by several pathophysiological features, such as allergen induced bronchoconstriction (in allergic asthma), airway hyperresponsiveness (AHR), airway inflammation, airway remodeling and mast cell hyperplasia. An increase of mast cells has been found in asthma patients. However, how these cells are involved in the development of asthma are not well defined. To investigate the role of mast cells in the pathophysiological characteristics of asthma, we established asthma models in guinea pigs, which have many similarities with humans, by exposing the animals to human relevant allergens: house dust mite (HDM) and cat dander extract (CDE). The involvement of mast cells in asthma-like features was investigated either by the addition of mast cell mediator antagonists or inhibitors, or inducing mast cell death. In paper I, we repeatedly exposed guinea pigs to HDM via intranasal instillation for seven weeks and successfully recaptured the antigen induced bronchoconstriction, the production of HDM specific immunoglobulins, AHR, eosinophilic inflammation with an increase of IL-13, airway remodeling (e.g., subepithelial collagen deposition and goblet cell hyperplasia) and mast cell hyperplasia. This model can be further used to study the role of mast cells in asthma. In paper II, we exposed guinea pigs to HDM or CDE intranasally for different time. Both HDM and CDE induce airway inflammation and airway remodeling after 4 weeks’ antigen exposures. These increases maintained after 8- and 12-week exposures. Exposing to both antigens for 8 weeks and 12 weeks induced a clear expansion of mast cells which is predominated by mast cells expressing tryptase. An increase of mast cells expressing both tryptase and chymase were also observed. In paper III, we isolated guinea pig trachea for comparing the effect of different mast cell agonists (HDM and Compound 48/80 (C48/80)) on airway smooth muscle responses and mediator release. We found that histamine, prostaglandins and 5- lipoxygenase products mediated the bronchoconstriction induced by HDM and C48/80. Both agonists induced a release of histamine, prostaglandin D2 and leukotriene B4. However, distinct of lipid mediator profiles were observed. The leukotriene E4 was only elevated by HDM, whereas C48/80 induced a broader release of lipid mediators. In paper IV and V, we identified an antibiotic monensin that can induce mast cell death. To examine if monensin can be a tool for investigating the role of mast cells in asthma, we cultured guinea pig tracheal segments from HDM sensitized guinea pigs and human bronchi with different concentrations of monensin for different time. We found that monensin has robust effects on causing mast cell death and totally blocked the HDM (in guinea pig trachea) and anti-IgE (in human bronchi) induced bronchoconstriction after 2 to 72h exposure without affecting the general tissue viability at low concentration. In the in vivo investigations, we exposed the guinea pigs to HDM repeatedly with or without monensin interventions. Monensin reduced the AHR, airway inflammation and mast cell hyperplasia in the HDM induced guinea pig model. In conclusion, exposing to human relevant allergens (HDM and CDE) are suitable for modeling of allergic asthma in guinea pigs. The increase of mast cells by HDM and CDE helps to investigate the role of mast cells in asthma models. Mast cells in guinea pig airways can respond differently to antigen and non-antigen agonists. Monensin can be a robust tool to induce mast cell death. The antigen induced bronchoconstriction by HDM in guinea pig trachea and anti-IgE in human bronchi are purely mast cell mediated. Our findings emphasize that mast cells have important roles in the development of AHR and airway inflammation in the guinea pig model used in this PhD study. The findings in this thesis highlight the importance of mast cells in asthma and the models we developed can be used as important tools for defining the mechanisms behind asthma

Regular treatment with formoterol for chronic asthma: serious adverse events

Epidemiological evidence has suggested a link between beta(2)-agonists and increases in asthma mortality. There has been much debate about possible causal links for this association, and whether regular (daily) long-acting beta2-agonists are safe.ObjectivesThe aim of this review is to assess the risk of fatal and non-fatal serious adverse events in trials that randomised patients with chronic asthma to regular formoterol versus placebo or regular short-acting beta2-agonists.Search methodsWe identified trials using the Cochrane Airways Group Specialised Register of trials. We checked websites of clinical trial registers for unpublished trial data and Food and Drug Administration (FDA) submissions in relation to formoterol. The date of the most recent search was January 2012.Selection criteriaWe included controlled, parallel design clinical trials on patients of any age and severity of asthma if they randomised patients to treatment with regular formoterol and were of at least 12 weeks' duration. Concomitant use of inhaled corticosteroids was allowed, as long as this was not part of the randomised treatment regimen.Data collection and analysisTwo authors independently selected trials for inclusion in the review. One author extracted outcome data and the second author checked them. We sought unpublished data on mortality and serious adverse events.Main resultsThe review includes 22 studies (8032 participants) comparing regular formoterol to placebo and salbutamol. Non-fatal serious adverse event data could be obtained for all participants from published studies comparing formoterol and placebo but only 80% of those comparing formoterol with salbutamol or terbutaline.Three deaths occurred on regular formoterol and none on placebo; this difference was not statistically significant. It was not possible to assess disease-specific mortality in view of the small number of deaths. Non-fatal serious adverse events were significantly increased when regular formoterol was compared with placebo (Peto odds ratio (OR) 1.57; 95% CI 1.06 to 2.31). One extra serious adverse event occurred over 16 weeks for every 149 people treated with regular formoterol (95% CI 66 to 1407 people). The increase was larger in children than in adults, but the impact of age was not statistically significant. Data submitted to the FDA indicate that the increase in asthma-related serious adverse events remained significant in patients taking regular formoterol who were also on inhaled corticosteroids.No significant increase in fatal or non-fatal serious adverse events was found when regular formoterol was compared with regular salbutamol or terbutaline.Authors' conclusionsIn comparison with placebo, we have found an increased risk of serious adverse events with regular formoterol, and this does not appear to be abolished in patients taking inhaled corticosteroids. The effect on serious adverse events of regular formoterol in children was greater than the effect in adults, but the difference between age groups was not significant.Data on all-cause serious adverse events should be more fully reported in journal articles, and not combined with all severities of adverse events or limited to those events that are thought by the investigator to be drug-related

ERS International congress, Madrid, 2019: Highlights from the General Pneumology Assembly

This article contains highlights and a selection of the scientific advances from the European Respiratory Society's General Pneumology Assembly that were presented at the 2019 European Respiratory Society International Congress in Madrid, Spain. The most relevant topics from the different groups will be discussed, covering a wide range of areas including rehabilitation and chronic care, general practice and primary care and M-health and E-health. In this review, the newest research and actual data as well as award-winning abstracts and highlight sessions will be discussed

Exercise-induced respiratory symptoms in childhood.

Background Exercise-induced symptoms (EIS) are common in childhood and can lead to physical activity avoidance, reduced quality of life, and overtreatment with inhaled corticosteroids if mistakenly diagnosed as asthma. Diagnosis of EIS can be difficult because different aetiologies share similar clinical presentations. Reported symptoms can be helpful to identify the correct diagnosis, as certain symptoms are typically associated with specific diagnoses (e.g. expiratory wheeze for exercise-induced bronchoconstriction, and throat tightness for inducible laryngeal obstruction (ILO)). Only few studies have investigated diagnosis, diagnostic evaluations, and reported symptoms in children with EIS. Aims: The overall aim of this PhD thesis were to gain epidemiological knowledge about diagnosis, diagnostic investigations, and reported symptoms in children with EIS. Specifically, I aimed to 1) set up a prospective study including children referred to paediatric respiratory outpatient clinics with respiratory symptoms 2) study diagnosis, diagnostic investigations and management in children referred for EIS 3) study if parent reported EIS are helpful to distinguish different diagnoses and 4) study EIS reported by physicians in the clinical history and assess agreement with parent-reported symptoms. 5) Additionally, I aimed to validate a model to predict asthma in preschool children. Methods To address the aims of this PhD thesis, I used data from the Swiss Paediatric Airway Cohort (SPAC), a longitudinal observational clinical study of children referred with respiratory symptoms to paediatric respiratory outpatient clinics in Switzerland. I used data from medical records to get information on referral diagnosis, final diagnosis, diagnostic investigations and proposed management from the outpatient clinics. I used data from parental questionnaires to get information about symptoms. For publication 5, I used data from the Leicestershire Respiratory Cohort (LRC) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Results The main body of this thesis consists of 5 articles (2 published, 1 in review, and 2 to be submitted). These are the main findings in summary: Publication 1: The SPAC study is a novel longitudinal observational cohort study of children with respiratory symptoms. By January 7, 2020, the SPAC study includes 1893 children 5 recruited from 10 pulmonology clinics. The SPAC study will provide real-life data from paediatric pulmonology clinics in Switzerland and will serve as a platform for nested studies. Publication 2: Diagnosis given at the paediatric respiratory outpatient clinic differed from suspected referral diagnosis in half of the children referred primarily for EIS. Dysfunctional breathing was a common diagnosis at the outpatient clinic but rarely suspected at time of referral. Diagnostic evaluation, management, and follow-up were inconsistent between clinics and diagnostic groups. Publication 3: Parent reported EIS (including information on type of symptoms, activities triggering EIS, and characteristics of symptoms) can help to distinguish different diagnoses in children seen with EIS. Publication 4: Physicians reported EIS in the medical records in almost all children referred for EIS. Activities triggering EIS and characteristics of EIS (e.g. localisation of symptoms, respiratory phase, and onset and duration of symptoms) were reported only in around half of the children. Agreement with parent questionnaire reported EIS ranged from poor to moderate. Publication 5: PARC predicted asthma at school age equally well in the validation cohort, ALSPAC (AUC 0.77), compared with the development cohort, LRC (AUC 0.78). Apart from severity of wheeze and cough, family history of symptoms, age, and sex, also exercise as trigger for respiratory symptoms predicted asthma at school age in the development and validation cohort. The discriminative ability of the PARC appeared to be robust to changes in inclusion criteria, scoring variables, and outcome definitions. PARC may need recalibration when applied in other populations. Additionally, I contributed to further publications, which are included in this PhD thesis as related publications. Conclusion In summary, diagnosis, diagnostic investigations, and management in children with EIS differed between outpatient clinics and diagnosis groups, indicating a need for diagnostic guidelines. Parental reported symptoms can help to distinguish diagnoses in children with EIS. Future studies should focus on developing an algorithm for diagnosing children seen with EIS including both reported symptoms and objective diagnostic tests.

Investigations into the physiological basis of the sensation of breathlessness in man

Imperial Users onl