Systems biology and asthma in children-latest progress in understanding asthma

Telemedicine is a particularly promising and evolving sector. Its importance has been recognized at both the national and international level. In France, this innovation is defined as a form of remote medical practice. It allows doctors and paramedics to be in close contact with the patient. Telemedicine encompasses 5 branches: teleconsultation, tele-expertise, medical regulation, tele-assistance, and tele-monitoring. The latter is intended to enable a medical professional to interpret remotely the data necessary for the medical monitoring of a patient and, where appropriate, to take decisions relating to the care of that patient. According to the WHO's first global strategy for digital health,1 digital technologies are an essential component and an enabler of sustainable health systems which helps develop universal health coverage;the appropriate use of digital technologies supports equity in access to digital resources so that no one is left behind. Different devices are now available to monitor cough (microphones), lung function (electronic home spirometers with automatic data storage), airflow (a vortex whistle producing a high-pitched sound), adherence to therapy (Bluetooth inhaler devices), nocturnal physiological changes (contactless bed sensors), breathing (smart shirts and radios, necklaces), FeNO, etc. The devices may be used by various means: solely by the patient (self-management), with retrospective analysis of data by the medical team during outpatient clinics, and/or for remote home or school feedback to a health-care team between visits to the clinic, or an autonomous 'expert' system (artificial intelligence). Cystic Fibrosis (CF) In many CF centers, the management strategy of bacterial infection has evolved from planned regular short I.V. antibiotic courses, to prolonged inhaled coupled with as needed oral and/or I.V. antibiotics. It is essential to treat pulmonary exacerbations (PEx) early since loss of FEV1 may be permanent. Exacerbations also contribute to morbidity and reduced health-related quality of life. With this in mind, close tele-monitoring of lung function is important. Telehealth spirometry assessments for children with CF living in a regional setting are feasible.2,3 In one study conducted in Melbourne, Australia, spirometry was successful in 55 of 59 (93%) attempted sessions. This equated to a travel time saving of 5h34mn/hospital visit.4 The combination of home monitor FEV1%pred and Respiratory Symptom Score (RSS) was helpful to predict a PEx in children with CF aged 5-19 years.4 During this one-year prospective multicenter study, 49 children were asked to use a home monitor 3 times a week. In the 2 weeks before a PEx, the RSS of the home monitor increased (p = 0.051). The FEV1%pred did not deteriorate in the 4 weeks before a PEx. Nevertheless, the FEV1%pred at the start of exacerbation was significantly lower than the FEV1%pred in the non-exacerbation group (mean difference 16.3%, p = 0.012). The combination of FEV1%pred and RSS had a sensitivity to predict an exacerbation of 92.9% (CI 75.0- 98.8%) and a specificity of 88.9% (CI 50.7-99.4%).4 Such promising results were not observed in a large multicenter RCT, the eICE (early intervention in CF exacerbation) trial, in which twice weekly home spirometry and respiratory symptom scoring were monitored. Patients were contacted by the CF team if a reduction in FEV1 >10% or an increase in respiratory symptoms was seen. The early intervention group had a shorter time to first exacerbation and more exacerbation treatments compared with the control group;however, this was not associated with a slower FEV1 decline. The trial was stopped early for futility, as completing it was unlikely to show a difference in primary endpoint. However, adherence to tele-monitoring over 52 weeks was suboptimal: 50% of patients transmitted data once per week and only 19% twice per week as per the protocol. This is in contrast to another study indicating that frequent home pulmonary function test monitoring could successfully improve medication adherence wit out significantly impacting treatment burden in CF adolescents aged 12-21 years with CF.5 These patients measured their lung function weekly for 1 year. Mean medication possession ratio was 60% in the previous year and 65% during the study (p=0.04). Mean treatment burden scaled score on the CFQ-R was 68 at enrollment and 66 at study completion (p=0.14).5 Overall, despite the large number of articles involving digital technology in CF, most are small pilot and intervention studies without comparators and there are very few RCTs. Although ongoing studies may yield some positive results, the majority so far have shown limited evidence to support the use of digital technology. A potentially exciting area of development is the use of digital technology to assist in the self-management of medications, or to define more precisely timing of more invasive treatments, e.g. to decrease overall antibiotic I.V. use. With this in mind, in a preliminary real-life study,we determined the feasibility and impact of tele-monitoring by portable spirometry (Spirobank Smart, Mir∗) supervised by a physiotherapist in children with CF aged 6-18 years with chronic Pseudomonas aeruginosa colonization requiring regular antibiotics. Median FEV1% was 62 [range, 43-111]. Clinical symptoms (body weight, SpO2, cough, tiredness, fever, loss of appetite, hemoptysis) were prospectively transmitted to the regional respiratory network, which alerted the pediatric CF center whenever FEV1 decline was accompanied by clinical Pex criteria. Patients accomplished an average of 6.3 spirometry tests/week (70% observance), and 3423 spirometry results with clinical questionnaires were teletransmitted. The regional network alerted the CF center in 33 cases, with a need for I.V. antibiotics in 5 cases. THC led to the safe avoidance of 130 days (-35%) of I.V. antibiotics compared to the previous year.2 In the longer term (2019-2021), 272 patients with CF have been recruited and are now being followed within our network. On average, each patient transmits data an average of 2.1 times/week;this rate decreases to 1.4 tele-transmissions/week/patient during the months of August and January. Ninety-two percent of children adhere correctly to the program (65% of cases: >3 spirometry tests/week and 27%: 1 to 3/ week). This sustained rate of adherence may be explained by supervision by home-based physiotherapists, and the possibility for patients to see their own FEV1 curves. Overall, in 2019 and 2020, the network has examined respectively 10,120 and 15,177 tele-transmitted clinical and spirometry signals. During the COVID-19 pandemic period, tele-transmissions peaked at 2.4 spirometry tests/week leading to the identification of 40 alerts and the administration of 15 antibiotic courses for severe exacerbation, thus avoiding FEV decline. In addition, THC facilitated the monitoring of patients in this new therapeutic area: the follow-up of very severe oxygendependent patients undergoing NIV with a baseline ppFEV 15 % improvement within the first 15 days of TRIKAFTA∗ treatment. Asthma It has previously been shown in children aged 6-18 years that there was low agreement between asthma control based on GINA criteria by means of prospective home monitoring, and the hospital asthma control questionnaire (ACQ). The former detected more cases of less well-controlled asthma than the latter.6 The results of clinical studies have been inconsistent. For example, on one hand, home monitoring of nocturnal physiological changes was successful in predicting asthma exacerbations7 in asthmatic children aged 5-18 years. The model on the full cohort performed with a sensitivity of 47.2%, specificity of 96.3%, and accuracy of 87.4%. On the other hand, a treatment strategy based on daily FEV1 monitoring over 12 months with medical feedback did not reduce severe asthma exacerbations in 50 children aged 6-16 years with severe uncontrolled allergic asthma.8 There were no significant differences between the 2 groups for unscheduled visits, lung function, QOL scores and daily inhaled cor icosteroids. Overall, Cochrane systematic reviews do not support the widespread implementation of tele-monitoring with healthcare provider feedback between clinic visits.9 Larger pragmatic studies could better determine the benefits of these interventions.