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The urgent need for effective treatments for acute and chronic lung diseases underscores the significance of developing innovative preclinical human research tools. The 2023 ATS Workshop on Precision Cut Lung Slices (PCLS) brought together 35 experts to discuss and address the role of human tissue-derived PCLS as a unique tool for target and drug discovery and validation in pulmonary medicine. With increasing interest and usage, along with advancements in methods and technology, there is a growing need for consensus on PCLS methodology and readouts. The current document recommends standard reporting criteria and emphasizes the requirement for careful collection and integration of clinical metadata. We further discuss current clinically relevant readouts that can be applied to PCLS and highlight recent developments and future steps for implementing novel technologies for PCLS modeling and analysis. The collection and correlation of clinical metadata and multiomic analysis will further advent the integration of this preclinical platform into patient endotyping and the development of tailored therapies for lung disease patients.

Motivation: Phecodes are widely used and easily adapted phenotypes based on International Classification of Diseases codes. The current version of phecodes (v1.2) was designed primarily to study common/complex diseases diagnosed in adults; however, there are numerous limitations in the codes and their structure., Results: Here, we present phecodeX, an expanded version of phecodes with a revised structure and 1,761 new codes. PhecodeX adds granularity to phenotypes in key disease domains that are under-represented in the current phecode structure-including infectious disease, pregnancy, congenital anomalies, and neonatology-and is a more robust representation of the medical phenome for global use in discovery research., Availability and Implementation: phecodeX is available at https://github.com/PheWAS/phecodeX., (© The Author(s) 2023. Published by Oxford University Press.)

Introduction: Chronic lung disease, that is, bronchopulmonary dysplasia (BPD) is the most common complication in preterm infants and develops as a consequence of the misguided formation of the gas-exchange area undergoing prenatal and postnatal injury. Subsequent vascular disease and its progression into pulmonary arterial hypertension critically determines long-term outcome in the BPD infant but lacks identification of early, disease-defining changes., Methods: We link impaired bone morphogenetic protein (BMP) signalling to the earliest onset of vascular pathology in the human preterm lung and delineate the specific effects of the most prevalent prenatal and postnatal clinical risk factors for lung injury mimicking clinically relevant conditions in a multilayered animal model using wild-type and transgenic neonatal mice., Results: We demonstrate (1) the significant reduction in BMP receptor 2 (BMPR2) expression at the onset of vascular pathology in the lung of preterm infants, later mirrored by reduced plasma BMP protein levels in infants with developing BPD, (2) the rapid impairment (and persistent change) of BMPR2 signalling on postnatal exposure to hyperoxia and mechanical ventilation, aggravated by prenatal cigarette smoke in a preclinical mouse model and (3) a link to defective alveolar septation and matrix remodelling through platelet derived growth factor-receptor alpha deficiency. In a treatment approach, we partially reversed vascular pathology by BMPR2-targeted treatment with FK506 in vitro and in vivo., Conclusion: We identified impaired BMP signalling as a hallmark of early vascular disease in the injured neonatal lung while outlining its promising potential as a future biomarker or therapeutic target in this growing, high-risk patient population., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The COVID-19 pandemic has presented significant safety concerns for healthcare providers, especially those performing aerosol-generating procedures. Several surgical societies issued early warnings that aerosols generated during minimally invasive surgery (MIS) could harbor infectious quantities of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). This study tested the hypothesis that MIS-aerosols contain SARS-CoV-2., Methods: To evaluate SARS-CoV-2 presence in aerosols emitted during intracavitary MIS, children <18 years who required emergent MIS and were discovered to be SARS-CoV-2-positive were enrolled. Swabs were obtained from the port in-line with a filtered smoke evacuation system, the tubing adjacent to this port, the fluid collection chamber and filter, and the distal endotracheal tube (ETT). All swabs were analyzed for SARS-CoV-2 using quantitative reverse-transcription polymerase chain reaction. To evaluate viral distribution in tissues, fluorescence in situ hybridization for SARS-CoV-2 was performed on resected specimens. Outcomes were recorded, and participating healthcare workers were tracked for SARS-CoV-2 conversion., Results: From July 1, 2020, to June 30, 2021, 11 children requiring emergent MIS were discovered preoperatively to be SARS-CoV-2 positive (median age: 14 years [5-17]). SARS-CoV-2 was detected only in ETT swabs and not in surgical aerosols or specimens. Median operative time was 56.5 minutes (IQR: 46-66), and postoperative stay was 21.2 hours (IQR: 1.97-57.57). No complications or viral eruption were recorded, and none of 63 healthcare workers tested positive for SARS-CoV-2 within 6 weeks., Discussion: SARS-CoV-2 was detected only in ETT secretions and not in surgical aerosols or specimens among a pediatric cohort of asymptomatic patients having emergent MIS.

Infants suffering from neonatal chronic lung disease, i.e., bronchopulmonary dysplasia, are facing long-term consequences determined by individual genetic background, presence of infections, and postnatal treatment strategies such as mechanical ventilation and oxygen toxicity. The adverse effects provoked by these measures include inflammatory processes, oxidative stress, altered growth factor signaling, and remodeling of the extracellular matrix. Both, acute and long-term consequences are determined by the capacity of the immature lung to respond to the challenges outlined above. The subsequent impairment of lung growth translates into an altered trajectory of lung function later in life. Here, knowledge about second and third hit events provoked through environmental insults are of specific importance when advocating lifestyle recommendations to this patient population. A profound exchange between the different health care professionals involved is urgently needed and needs to consider disease origin while future monitoring and treatment strategies are developed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Sucre, Haist, Bolton and Hilgendorff.)

Purpose: To study the relationship between central hypotonia and motor development, and to determine the relative contribution of nuchal, truncal, and appendicular hypotonia domains to motor development., Methods: Appendicular, nuchal, and truncal tones of high-risk infants were assessed, as was their psychomotor developmental index (PDI). Infants with peripheral hypotonia were excluded., Results: We included 164 infants (mean age 9.6 ± 4 months), 36 with normal tone in all 3 domains and 128 with central hypotonia. Twenty-six of the latter had hypotonia in 1 domain and 102 had multiple combinations of 3 domains. Hypotonia domains were distributed as follows: truncal (n = 115), appendicular (n = 93), and nuchal (n = 70). Each domain was significantly associated with PDI scores (P < .001) but not with a later diagnosis of cerebral palsy. On linear regression, nuchal hypotonia had the strongest contribution to PDI scores (β = -0.6 [nuchal], -0.45 [appendicular], and -0.4 [truncal], P < .001)., Conclusions: Central hypotonia, especially nuchal tone, is associated with lowered motor development scores.