Unravelling the respiratory health path across the lifespan for survivors of preterm birth.

Many survivors of preterm birth will have abnormal lung development, reduced peak lung function and, potentially, an increased rate of physiological lung function decline, each of which places them at increased risk of chronic obstructive pulmonary disease across the lifespan. Current rates of preterm birth indicate that by the year 2040, around 50 years since the introduction of surfactant therapy, more than 700 million individuals will have been born prematurely-a number that will continue to increase by about 15 million annually. In this Personal View, we describe current understanding of the impact of preterm birth on lung function through the life course, with the aim of putting this emerging health crisis on the radar for the respiratory community. We detail the potential underlying mechanisms of prematurity-associated lung disease and review current approaches to prevention and management. Furthermore, we propose a novel way of considering lung disease after preterm birth, using a multidimensional model to determine individual phenotypes of lung disease-a first step towards optimising management approaches for prematurity-associated lung disease.

Lung clearance index in children with cystic fibrosis previously diagnosed with CRMS/CFSPID: A monocentric prospective experience.

INTRODUCTION: No data are available on the values and role of lung clearance index (LCI) in cystic fibrosis (CF) Screen Positive Inconclusive Diagnosis (CFSPID) progressed to CF diagnosis (CFSPID > CF). This study aimed to assess the value of the LCI in correctly predicting the progression of CFSPID to CF. METHODS: This is a prospective study carried out at the CF Regional Center of Florence, Italy from September 1, 2019. We compared LCI values in children with CF diagnosed for positive newborn screening (NBS), CFSPID or CFSPID > CF for pathological sweat chloride (SC). The Exhalyzer-D (EcoMedics AG, Duernten, Switzerland, software version 3.3.1) was used to conduct the LCI tests, every 6 months on stable children. RESULTS: Forty-two cooperating children were enrolled (mean age at LCI tests: 5.4 years, range: 2.7-8.7): 26 (62%) had CF, 8 (19%) were CFSPID > CF for positive SC, while 8 (19%) kept the CFSPID label at last LCI test. The mean LCI value for patients with CF (7.39; 5.98-10.24) was statistically higher compared to both the mean LCI in the CFSPID > CF (6.62; 5.69-7.58) and in CFSPID (6.56; 5.64-7.21). CONCLUSIONS: Most of asymptomatic CFSPID or progressed to CF have normal LCI. Further data on the longitudinal course of LCI during follow up of CFSPID and on larger cohorts is needed.

Bronchodilator response by interrupter technique to guide management of preschool wheeze.

OBJECTIVE: We examined relationships between clinical features and pulmonary function before and after inhaled corticosteroid (ICS) treatment in wheezy preschool children, and specifically, whether measuring bronchodilator response (BDR) could predict benefit from ICS. DESIGN: Clinical non-randomised intervention study SETTING: Secondary care. PATIENTS: Preschool children (2 years to <6 years) with recurrent wheeze. INTERVENTIONS: Inhaled beta-agonist, ICS. OUTCOME MEASURES: We measured prebronchodilator and postbronchodilator interrupter resistance (Rint) and symptom scores at 0 (V1), 4 (V2) and 12 (V3) weeks. At V2, those with a predetermined symptom level commenced ICS. Modified Asthma Predictive Index (mAPI) and parental perception of response to bronchodilator were recorded. Response to ICS was defined as a reduction in daily symptom score of >0.26. Positive BDR was defined as fall in Rint of ≥0.26 kPa.s/L, ≥35% predicted or ≥1.25 Z Scores. RESULTS: Out of 138 recruited children, 67 completed the full study. Mean (SD) prebronchodilator Rint at V2 was 1.22 (0.35) kPa.s/L, and fell after starting ICS (V3) to 1.09 (0.33) kPa.s/L (p<0.001), while mean (SD) daily symptom score fell from 0.56 (0.36) to 0.28 (0.36) after ICS (p<0.001). Positive Rint BDR before ICS (at V1 and/or V2), using all three threshold criteria, was significantly associated with response to ICS on symptom scores at V3 (p<0.05). mAPI was not significantly associated with response to ICS, and parents' perception of response to bronchodilator was not related to measured Rint BDR . CONCLUSIONS: Rint BDR may be helpful in selecting which wheezy preschool children are likely to benefit from ICS.

Chiral Single-Molecule Potentiometers Based on Stapled ortho- Oligo(phenylene)ethynylenes.

We report on the chemical design of chiral molecular junctions with stress-dependent conductance, whose helicity is maintained during the stretching of a single molecule junction due to the stapling of both ends of the inner helix. In the reported compounds, different conductive pathways are observed, with clearly different conductance values and plateau-length distributions, attributed to different conformations of the helical structures. The large chiro-optical responses and the potential use of these molecules as unimolecular spin filters have been theoretically proved using state-of-the-art Density Functional Theory (DFT) calculations, including a fully ab-initio estimation of the CISS-originating spin polarization which is done, for the first time, for a realistic molecular system.

Constrained DFT for Molecular Junctions.

We have explored the use of constrained density functional theory (cDFT) for molecular junctions based on benzenediamine. By elongating the junction, we observe that the energy gap between the ionization potential and the electronic affinity increases with the stretching distance. This is consistent with the trend expected from the electrostatic screening. A more detailed analysis shows how this influences the charge distribution of both the individual metal layers and the molecular atoms. Overall, our work shows that constrained DFT is a powerful tool for studying screening effects in molecular junctions.

International consensus on lung function testing during the COVID-19 pandemic and beyond.

Coronavirus disease 2019 (COVID-19) has negatively affected the delivery of respiratory diagnostic services across the world due to the potential risk of disease transmission during lung function testing. Community prevalence, reoccurrence of COVID-19 surges and the emergence of different variants of SARS-CoV-2 have impeded attempts to restore services. Finding consensus on how to deliver safe lung function services for both patients attending and for staff performing the tests are of paramount importance. This international statement presents the consensus opinion of 23 experts in the field of lung function and respiratory physiology balanced with evidence from the reviewed literature. It describes a robust roadmap for restoration and continuity of lung function testing services during the COVID-19 pandemic and beyond. Important strategies presented in this consensus statement relate to the patient journey when attending for lung function tests. We discuss appointment preparation, operational and environmental issues, testing room requirements including mitigation strategies for transmission risk, requirement for improved ventilation, maintaining physical distance and use of personal protection equipment. We also provide consensus opinion on precautions relating to specific tests, filters, management of special patient groups and alternative options to testing in hospitals. The pandemic has highlighted how vulnerable lung function services are and forces us to re-think how long-term mitigation strategies can protect our services during this and any possible future pandemic. This statement aspires to address the safety concerns that exist and provide strategies to make lung function tests and the testing environment safer when tests are required.

Clinical significance and applications of oscillometry.

Recently, "Technical standards for respiratory oscillometry" was published, which reviewed the physiological basis of oscillometric measures and detailed the technical factors related to equipment and test performance, quality assurance and reporting of results. Here we present a review of the clinical significance and applications of oscillometry. We briefly review the physiological principles of oscillometry and the basics of oscillometry interpretation, and then describe what is currently known about oscillometry in its role as a sensitive measure of airway resistance, bronchodilator responsiveness and bronchial challenge testing, and response to medical therapy, particularly in asthma and COPD. The technique may have unique advantages in situations where spirometry and other lung function tests are not suitable, such as in infants, neuromuscular disease, sleep apnoea and critical care. Other potential applications include detection of bronchiolitis obliterans, vocal cord dysfunction and the effects of environmental exposures. However, despite great promise as a useful clinical tool, we identify a number of areas in which more evidence of clinical utility is needed before oscillometry becomes routinely used for diagnosing or monitoring respiratory disease.

Lung function at school age in infants with lower respiratory tract infections with and without wheezing: A birth cohort study.

OBJECTIVE: To evaluate the relationship between lower respiratory tract infections (LRTI), in the first 2 years of life and lung function at school age in the Piccolipiù birth cohort (Italy). METHODS: Data on LRTI (doctor diagnosis of bronchitis, bronchiolitis, pneumonia) and wheezing (≥3 episodes or a diagnosis of asthmatic bronchitis) in the first 2 years of life were obtained from parental questionnaires. Lung function was assessed at 7 years by spirometry and forced volume vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, forced expiratory flow between 25% and 75%, and at 75% of FVC (FEF25-75 and FEF75 ) were reported as Z-scores. The associations between LRTI and spirometric variables were estimated with linear regression models. RESULTS: Among 877 children studied, 22.1% had LRTI only, 5.4% wheezing only, 13.2% had both, and 59.3% had neither LRTI nor wheezing. Children with LRTI had lower FVC and FEV1 than children without (Z-score differences: -0.18 [95% confidence intervals: -0.31; -0.06] and -0.15 [-0.27; -0.03]). When children were stratified by history of both LRTI and wheezing, there was no association between LRTI only and spirometric values. Conversely, having had both LRTI and wheezing was inversely associated with all lung function measures: Z-score differences of -0.24 (-0.42; -0.07); -0.42 (-0.59; -0.24); -0.25 (-0.41; -0.08); -0.37 (-0.54; -0.21); -0.30 (-0.46; -0.14) for FVC, FEV1, FEV1 /FVC, FEF25-75 and FEF75, respectively. CONCLUSION: Infants with wheezing and LRTI, but not those with LRTI only, had reduced lung function at school-age.

Severe pediatric asthma therapy: Omalizumab-A systematic review and meta-analysis of efficacy and safety profile.

Background: Omalizumab is the first biological therapy used to treat moderate-to-severe asthma and certainly the one with the highest number of publications. Methods: A systematic review and meta-analysis were performed to examine two critical outcomes of omalizumab therapy, asthma exacerbation rate, the reduction of the use of inhaled corticosteroids (ICS), and the improvement of the lung function as a secondary outcome using the following keywords in the MEDLINE database: "anti-IgE, severe asthma, children, and randomized controlled trial." We specifically selected papers that included moderate-to-severe asthma patients and collected data on children and adolescents. Results: Four RCT studies (total number of patients = 1,239) were included in the analysis. The reported data on exacerbations showed an overall improvement in the exacerbation rate with a decreased use of inhaled steroids and some other minimal clinically important difference (MCID). Conclusions: Our systematic review confirms the known findings that omalizumab therapy decreases asthma exacerbation rate and reduces background therapy inhaled steroid dose. Therefore, add-on therapy with omalizumab shows a good efficacy and safety profile, thus proving to be a useful additional therapeutic option. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023396785.

Artificial intelligence for quality control of oscillometry measures.

BACKGROUND: The forced oscillation technique (FOT) allows non-invasive lung function testing during quiet breathing even without expert guidance. However, it still relies on an operator for excluding breaths with artefacts such as swallowing, glottis closure and coughing. This manual selection is operator-dependent and time-consuming. We evaluated supervised machine learning methods to exclude breaths with artefacts from data analysis automatically. METHODS: We collected 932 FOT measurements (Resmon Pro Full, Restech) from 155 patients (6-87 years) following the European Respiratory Society (ERS) technical standards. Patients were randomly assigned to either a training (70%) or test set. For each breath, we computed 71 features (including anthropometric, pressure stimulus, breathing pattern, and oscillometry data). Univariate filter, multivariate filter and wrapper methods for feature selection combined with several classification models were considered. RESULTS: Trained operators identified 4333 breaths with- and 10244 without artefacts. Features selection performed by a wrapper method combined with an AdaBoost tree model provided the best performance metrics on the test set: Balanced Accuracy = 85%; Sensitivity = 79%; Specificity = 91%; AUC-ROC = 0.93. Differences in FOT parameters computed after manual or automatic breath selection was less than ∼0.25 cmH2O*s/L for 95% of cases. CONCLUSION: Supervised machine-learning techniques allow reliable artefact detection in FOT diagnostic tests. Automating this process is fundamental for enabling FOT for home monitoring, telemedicine, and point-of-care diagnostic applications and opens new scenarios for respiratory and community medicine.

COVID-19 Pandemic and Reduced Physical Activity: Is There an Impact on Healthy and Asthmatic Children?

Physical activity (PA) has been seen to improve asthma symptoms, lung function, and quality of life, as well as to reduce airway inflammation and bronchial responsiveness. As a consequence of the COVID-19 pandemic, the minimal amount of PA recommended by the World Health Organization-i.e., about 60 min/day of moderate-to-high intensity-is difficult to achieve for many children, particularly those living in urban areas. Short-term changes in PA because of the COVID-19 pandemic may become habitual, increasing the risk of adverse asthma outcomes in children. Indeed, prolonged home confinement during the COVID-19 pandemic reduces PA levels and increases sedentary behaviors, possibly impairing immune system function and increasing susceptibility to inflammatory diseases. However, there is limited evidence regarding the effects of lockdown due to COVID-19 on PA and sedentary behaviors in asthmatic children. Given that children stay longer indoors, indoor air pollution represents a major issue to consider during home confinement. This narrative review aims to summarize the available evidence about the impact of decreased PA and increased sedentary behaviors on children with asthma during the COVID-19 pandemic. In addition, strategies for supporting PA in children with asthma during the COVID-19 pandemic are suggested, also looking at the issue of indoor air quality.

Self-administration of omalizumab: why not? A literature review and expert opinion.

Introduction: Omalizumab is used to treat severe uncontrolled allergic asthma and chronic spontaneous urticaria (CSU), and is approved for self-administration in prefilled syringes. It is thus important to understand the advantages, critical issues, and indications for home administration.Areas covered: The present review summarizes the available evidence on home administration of omalizumab in asthma and CSU to illustrate the advantages derived from self-administration of patients in this setting.Expert opinion: The available data suggest that patients can safely administer biologics at home with suitable training, and that home administration is time saving and cost-effective. The majority of patients with severe asthma or CSU treated with omalizumab are likely to be suitable candidates for self-administration, which can be proposed to anyone that the clinician deems suitable. In addition to clinicians, pharmacists can also play a key role in managing patients who are prescribed home administration. A practical flow chart is proposed on selection of patients and their management during home administration. Self-administration of biologics can be considered as a valid alternative to traditional injections in a clinical setting, and the evidence has shown that no major issues need to be overcome in terms of safety or efficacy.

Impact of a supervised training course on spirometry competency for primary care pediatricians.

OBJECTIVE: Spirometry is the most commonly performed lung function test, and performance, adherence to acceptability and repeatability criteria, and accurate interpretation of results help optimize the test's usefulness. This study aimed to measure the effects of spirometry training courses supported by the Italian Pediatric Respiratory Society (IPRS) on primary care pediatricians' (PCP) knowledge of spirometry test quality, ability to interpret results, and overall degree of satisfaction with the course. METHODS: Of the six face-to-face courses, four lasted two days and two lasted one day: mean duration of theoretical lessons was five and four hours respectively; and practical sessions lasted eight and six hours, respectively. At the end of each course, participants took a learning test consisting of evaluating six flow-volume curves. Degree of satisfaction was assessed by asking participants to rank the relevance, quality, and usefulness of the course. RESULTS: 261 PCPs were involved, with most (67.43%) taking two-day courses. Nearly all participants correctly identified normal and restrictive patterns. Intrathoracic large-airway obstruction was the pattern most difficult to identify correctly (70.5% overall), whereas > 80% of the participants correctly classified artifacts, obstructive-restrictive, and obstructive patterns. Participants in longer courses reported significantly higher values on the learning score. The overall degree of satisfaction average ranged between "good" and "excellent". CONCLUSIONS: This pilot study showed the greater impact of two-day courses than one-day courses for training PCPs to properly interpret spirometry, confirming that a practical module lasting at least six hours is sufficient to deliver adequate training on spirometry for healthcare professionals.

Epithelial dysfunction, respiratory infections and asthma: the importance of immunomodulation. A focus on OM-85.

INTRODUCTION: Damage to the respiratory epithelium, is often a multifactorial phenomenon. The risk for developing a damage in respiratory epithelium and recurrent respiratory infections may vary among individuals. Preventive measures are based on strengthening the immune function, thus increasing the natural response to pathogens. Immunomodulatory agents are: i. synthetic molecules; ii. Probiotics, prebiotics, symbiotics; iii. Lysates, bacterial extracts immunomodulators: OM-85, RU 41740, D53; iv. Trace elements, vitamins. OM-85 is used for the prevention of recurrent respiratory tract infections and/or exacerbations both in adults and children, showing a good efficacy and safety profile. Its active principle, an extract of bacterial lysates isolated from 21 known respiratory pathogenic strains, shows protection against airway infections of bacterial and viral origin. AREAS COVERED: This non-systematic review focuses on bacterial lysates and in particular on OM-85 and its effects on respiratory epithelium function and activity in asthma respiratory infections. Studies were selected by PubMed search of "bacterial lysate" or "OM-85" and "respiratory epithelium" or "respiratory infections", from 1993 to 2019. EXPERT OPINION: Results highlight the ability of OM-85 to trigger immunomodulatory and protective immune responses against different pathogens in vivo, including influenza and respiratory syncytial virus as well bacterial superinfection following influenza.

Pulmonary function testing in children's interstitial lung disease.

The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome.PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials.

Fetal Origins of Asthma: A Longitudinal Study from Birth to Age 36 Years.

Rationale: Deficits in infant lung function-including the ratio of the time to reach peak tidal expiratory flow to the total expiratory time (tptef/te) and maximal expiratory flow at FRC (V̇maxFRC)-have been linked to increased risk for childhood asthma.Objectives: To examine the individual and combined effects of tptef/te and V̇maxFRC in infancy on risk for asthma and abnormalities of airway structure into mid-adult life.Methods: One hundred eighty participants in the Tucson Children's Respiratory Study birth cohort had lung function measured by the chest-compression technique in infancy (mean age ± SD: 2.0 ± 1.2 mo). Active asthma was assessed in up to 12 questionnaires between ages 6 and 36 years. Spirometry and chest high-resolution computed tomographic (HRCT) imaging were completed in a subset of participants at age 26. The relations of infant tptef/te and V̇maxFRC to active asthma and airway structural abnormalities into adult life were tested in multivariable mixed models.Measurements and Main Results: After adjustment for covariates, a 1-SD decrease in infant tptef/te and V̇maxFRC was associated with a 70% (P = 0.001) and 55% (P = 0.005) increased risk of active asthma, respectively. These effects were partly independent, and two out of three infants who were in the lowest tertile for both tptef/te and V̇maxFRC developed active asthma by mid-adult life. Infant V̇maxFRC predicted reduced airflow and infant tptef/te reduced HRCT airway caliber at age 26.Conclusions: These findings underscore the long-lasting effects of the fetal origins of asthma, support independent contributions by infant tptef/te and V̇maxFRC to development of asthma, and link deficits at birth in tptef/te with HRCT-assessed structural airway abnormalities in adult life.

Italian pediatric respiratory society recommendations on pediatric pulmonary function testing during COVID-19 pandemic.

BACKGROUND: Effective prevention and control strategies are mandatory to prevent SARS-CoV-2 infection. MAIN TEXT: The Italian Pediatric Respiratory Society promotes a series of new recommendations that should be followed in pulmonary function testing laboratories during the COVID-19 pandemic. CONCLUSION: Pulmonary function testing should be performed in children with chronic lung disease only if it is needed to guide management and limited to the necessary tests, namely spirometry. When performed, strict infection control measures should be followed due to the potential risk of transmitting SARS-CoV-2.

Brief report: International perspectives on the pediatric COVID-19 experience.

The 2019 novel coronavirus (SARS-CoV-2) is endangering human health worldwide; scarcity of published pediatric cases and current literature and the absence of evidence-based guidelines necessitate international sharing of experience and personal communication. On 31 March 2020 the International Committee of the American Thoracic Society Pediatrics Assembly recorded an online podcast, during which pediatric pulmonologists worldwide shared their experience on the novel coronavirus disease (COVID-19) in children. The aim was to share personal experience in organizing pediatric care in different health care settings globally, protecting health care workers, and isolation practices. This manuscript summarizes the common themes of the podcast which centered around three main topics: more benign clinical disease and progression in pediatric cases compared to adults, a strong need for strategies to protect health care workers, and social or economic disparities as a barrier to successful pandemic control.