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Background: Drug discovery strongly relies on the thorough evaluation of preclinical experimental studies. In the context of pulmonary fibrosis, micro-computed tomography (µCT) and histology are well-established and complementary tools for assessing, in animal models, disease progression and response to treatment. µCT offers dynamic, real-time insights into disease evolution and the effects of therapies, while histology provides a detailed microscopic examination of lung tissue. Here, we present a semi-automatic pipeline that integrates these readouts by matching individual µCT volume slices with the corresponding histological sections, effectively linking densitometric data with Ashcroft score measurements., Methods: The tool first geometrically aligns the vertical axis of the µCT volume with the cutting plane used to prepare the histological sample. Then, focusing on the left lung, it computes the affine registration that identifies the µCT coronal slice that best matches the histological section. Finally, quantitative µCT imaging parameters are extracted from the selected slice. In a proof-of-concept test, the tool was applied to a bleomycin-induced mouse model of lung fibrosis., Results: The proposed approach demonstrated high accuracy and time effectiveness in matching µCT and histological sections minimizing manual intervention, with an overall success rate of 95%, and reduced time required to align µCT and histological data from 40 to 5 min. Significant correlations were found between quantitative data derived from µCT and histology data., Conclusions: The precise combination of microscopic ex-vivo information with 3D in-vivo data enhances the accuracy and representativeness of tissue analysis and provides a structural context for omic studies, serving as the foundation for a multi-layer platform. By facilitating a detailed and objective view of disease progression and treatment response, this approach has the potential to accelerate the development of effective therapies for lung fibrosis., Competing Interests: Declarations Ethics approval and consent to participate All animal experiments described herein were authorized by the official competent authority and approved by the intramural animal-welfare body (AWB) of Chiesi Farmaceutici and authorized by the Italian Ministry of Health (protocol number: 449/2016-PR). All procedures were conducted in compliance with the European Directive 2010/63 UE, Italian D.Lgs 26/2014, the revised “Guide for the Care and Use of Laboratory Animals” and with the ‘Animal Research: Reporting of In Vivo Experiments’ (ARRIVE) guidelines. Consent for publication Not applicable. Competing interests FFS, GV and EF are employees of Chiesi Farmaceutici S.p.A., which supported the research work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential competing interests., (© 2024. The Author(s).)

Background: Idiopathic Pulmonary Fibrosis (IPF), prevalently affecting individuals over 60 years of age, has been mainly studied in young mouse models. The limited efficacy of current treatments underscores the need for animal models that better mimic an aged patient population. We addressed this by inducing pulmonary fibrosis in aged mice, using longitudinal micro-CT imaging as primary readout, with special attention to animal welfare., Methods: A double bleomycin dose was administered to 18-24 months-old male C57Bl/6j mice to induce pulmonary fibrosis. Bleomycin dosage was reduced to as low as 75% compared to that commonly administered to young (8-12 weeks-old) mice, resulting in long-term lung fibrosis without mortality, complying with animal welfare guidelines. After fibrosis induction, animals received Nintedanib once-daily for two weeks and longitudinally monitored by micro-CT, which provided structural and functional biomarkers, followed by post-mortem histological analysis as terminal endpoint., Results: Compared to young mice, aged animals displayed increased volume, reduced tissue density and function, and marked inflammation. This increased vulnerability imposed a bleomycin dosage reduction to the lowest tested level (2.5 µg/mouse), inducing a milder, yet persistent, fibrosis, while preserving animal welfare. Nintedanib treatment reduced fibrotic lesions and improved pulmonary function., Conclusions: Our data identify a downsized bleomycin treatment that allows to achieve the best trade-off between fibrosis induction and animal welfare, a requirement for antifibrotic drug testing in aged lungs. Nintedanib displayed significant efficacy in this lower-severity disease model, suggesting potential patient stratification strategies. Lung pathology was quantitatively assessed by micro-CT, pointing to the value of longitudinal endpoints in clinical trials., (© 2024. The Author(s).)

The need for faster and more accessible alternatives to laboratory microscopy is driving many innovations throughout the image and data acquisition chain in the biomedical field. Benchtop microscopes are bulky, lack communications capabilities, and require trained personnel for analysis. New technologies, such as compact 3D-printed devices integrated with the Internet of Things (IoT) for data sharing and cloud computing, as well as automated image processing using deep learning algorithms, can address these limitations and enhance the conventional imaging workflow. This review reports on recent advancements in microscope miniaturization, with a focus on emerging technologies such as photoacoustic microscopy and more established approaches like smartphone-based microscopy. The potential applications of IoT in microscopy are examined in detail. Furthermore, this review discusses the evolution of image processing in microscopy, transitioning from traditional to deep learning methods that facilitate image enhancement and data interpretation. Despite numerous advancements in the field, there is a noticeable lack of studies that holistically address the entire microscopy acquisition chain. This review aims to highlight the potential of IoT and artificial intelligence (AI) in combination with portable microscopy, emphasizing the importance of a comprehensive approach to the microscopy acquisition chain, from portability to image analysis.

Geometrical models of the airways offer a comprehensive perspective on the complex interplay between lung structure and function. Originating from mathematical frameworks, these models have evolved to include detailed lung imagery, a crucial enhancement that aids in the early detection of morphological changes in the airways, which are often the first indicators of diseases. The accurate representation of airway geometry is crucial in research areas such as biomechanical modeling, acoustics, and particle deposition prediction. This review chronicles the evolution of these models, from their inception in the 1960s based on ideal mathematical constructs, to the introduction of advanced imaging techniques like computerized tomography (CT) and, to a lesser degree, magnetic resonance imaging (MRI). The advent of these techniques, coupled with the surge in data processing capabilities, has revolutionized the anatomical modeling of the bronchial tree. The limitations and challenges in both mathematical and image-based modeling are discussed, along with their applications. The foundation of image-based modeling is discussed, and recent segmentation strategies from CT and MRI scans and their clinical implications are also examined. By providing a chronological review of these models, this work offers insights into the evolution and potential future of airway geometry modeling, setting the stage for advancements in diagnosing and treating lung diseases. This review offers a novel perspective by highlighting how advancements in imaging techniques and data processing capabilities have significantly enhanced the accuracy and applicability of airway geometry models in both clinical and research settings. These advancements provide unique opportunities for developing patient-specific models.

Idiopathic Pulmonary Fibrosis (IPF) is a debilitating and fatal lung disease characterized by the excessive formation of scar tissue and decline of lung function. Despite extensive research, only two FDA-approved drugs exist for IPF, with limited efficacy and relevant side effects. Thus, there is an urgent need for new effective therapies, whose discovery strongly relies on IPF animal models. Despite some limitations, the Bleomycin (BLM)-induced lung fibrosis mouse model is widely used for antifibrotic drug discovery and for investigating disease pathogenesis. The initial acute inflammation triggered by BLM instillation and the spontaneous fibrosis resolution that occurs after 3 weeks are the major drawbacks of this system. In the present study, we applied micro-CT technology to a longer-lasting, triple BLM administration fibrosis mouse model to define the best time-window for Nintedanib (NINT) treatment. Two different treatment regimens were examined, with a daily NINT administration from day 7 to 28 (NINT 7-28), and from day 14 to 28 (NINT 14-28). For the first time, we automatically derived both morphological and functional readouts from longitudinal micro-CT. NINT 14-28 showed significant effects on morphological parameters after just 1 week of treatment, while no modulations of these biomarkers were observed during the preceding 7-14-days period, likely due to persistent inflammation. Micro-CT morphological data evaluated on day 28 were confirmed by lung histology and bronchoalveolar lavage fluid (BALF) cells; Once again, the NINT 7-21 regimen did not provide substantial benefits over the NINT 14-28. Interestingly, both NINT treatments failed to improve micro-CT-derived functional parameters. Altogether, our findings support the need for optimized protocols in preclinical studies to expedite the drug discovery process for antifibrotic agents. This study represents a significant advancement in pulmonary fibrosis animal modeling and antifibrotic treatment understanding, with the potential for improved translatability through the concurrent structural-functional analysis offered by longitudinal micro-CT., (© 2024. The Author(s).)

Systemic sclerosis (SSc) with interstitial lung disease (SSc-ILD) lacks curative pharmacological treatments, thus necessitating effective animal models for candidate drug discovery. Existing bleomycin (BLM)-induced SSc-ILD mouse models feature spatially limited pulmonary fibrosis, spontaneously resolving after 28 days. Here, we present an alternative BLM administration approach in female C57BL/6 mice, combining oropharyngeal aspiration (OA) and subcutaneous mini-pump delivery (pump) of BLM to induce a sustained and more persistent fibrosis, while retaining stable skin fibrosis. A dose-finding study was performed with BLM administered as 10 µg (OA) +80 mg/kg (pump) (10 + 80), 10 + 100, and 15 + 100. Forty-two days after OA, micro-computed tomography (micro-CT) imaging and histomorphometric analyses showed that the 10 + 100 and 15 + 100 treatments induced significant alterations in lung micro-CT-derived readouts, Ashcroft score, and more severe fibrosis grades compared with saline controls. In addition, a marked reduction in hypodermal thickness was observed in the 15 + 100 group. A time-course characterization of the BLM 15 + 100 treatment at days 28 , 35 , and 42 , including longitudinal micro-CT imaging, revealed progressing alterations in lung parameters. Lung histology highlighted a sustained fibrosis accompanied by a reduction in hypodermis thickness throughout the explored time-window, with a time-dependent increase in fibrotic biomarkers detected by immunofluorescence analysis. BLM-induced alterations were partly mitigated by Nintedanib treatment. Our optimized BLM delivery approach leads to extensive and persistent lung fibrotic lesions coupled with cutaneous fibrotic alterations: it thus represents a significant advance compared with current preclinical models of BLM-induced SSc-ILD. NEW & NOTEWORTHY This study introduces an innovative approach to enhance the overall performance of the mouse bleomycin (BLM)-induced model for systemic sclerosis with interstitial lung disease (SSc-ILD). By combining oropharyngeal aspiration and subcutaneous mini-pump delivery of BLM, our improved model leads to sustained lung fibrosis and stable skin fibrosis in female C57BL/6 mice. The optimized 15 + 100 treatment results in extensive and persistent lung fibrotic lesions and thus represents a significant improvement over existing preclinical models of BLM-induced SSc-ILD.

It is a challenge to keep abreast of all the clinical and scientific advances in the field of respiratory medicine. This article contains an overview of laboratory-based science, clinical trials and qualitative research that were presented during the 2023 European Respiratory Society International Congress within the sessions from the five groups of Assembly 1 (Respiratory Clinical Care and Physiology). Selected presentations are summarised from a wide range of topics: clinical problems, rehabilitation and chronic care, general practice and primary care, electronic/mobile health (e-health/m-health), clinical respiratory physiology, exercise and functional imaging., Competing Interests: Conflict of interest: C-Y. Hui is a visitor at the University of Edinburgh and is a senior consultant in healthcare sustainability at Turner and Townsend. Her research with the University of Edinburgh is independent from, and not financially supported by, Turner and Townsend. Her views in this publication and the ERS Congress are her own, and not those of Turner and Townsend. Neither she, nor Turner and Townsend, stand to gain financially from work reported in this publication. Conflict of interest: C. Vicente reports personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Mylan, outside the submitted work. Conflict of interest: V. Poberezhets reports personal fees from AstraZeneca outside the submitted work. Conflict of interest: F.M.E. Franssen reports grants and personal fees from AstraZeneca, Chiesi, GlaxoSmithKline and Sanofi, and personal fees from Pieris, outside the submitted work. Conflict of interest: I. Vogiatzis is an associate editor of this journal. Conflict of interest: T. Gille reports personal fees from Roche SAS, outside the submitted work. Conflict of interest: The other authors have nothing to disclose., (Copyright ©The authors 2024.)

Background: High positive end-expiratory pressure (PEEP>10 cmH 2 O) is commonly used in mechanically ventilated hypoxemic patients with COVID-19. However, some epidemiological and physiological studies indirectly suggest that using a lower PEEP may primarily and beneficially decrease lung hyperinflation in this population. Herein we directly quantified the effect of decreasing PEEP from 15 to 10 cmH 2 O on lung hyperinflation and collapse in mechanically ventilated patients with COVID-19., Methods: Twenty mechanically ventilated patients with COVID-19 underwent a lung computed tomography (CT) at PEEP of 15 and 10 cmH 2 O. The effect of decreasing PEEP on lung hyperinflation and collapse was directly quantified as the change in the over-aerated (density below -900 HU) and non-aerated (density above -100 HU) lung volumes. The net response to decreasing PEEP was computed as the sum of the change in those two compartments and expressed as the change in the "pathologic" lung volume. If the pathologic lung volume decreased (i.e., hyperinflation decreased more than collapse increased) when PEEP was decreased, the net response was considered positive; otherwise, it was considered negative., Results: On average, the ratio of arterial tension to inspiratory fraction of oxygen (PaO 2 :FiO 2 ) in the overall study population was 137 (119-162) mmHg. In 11 (55%) patients, the net response to decreasing PEEP was positive. Their over-aerated lung volume decreased by 159 (98-186) mL, while the non-aerated lung volume increased by only 58 (31-91) mL. In nine (45%) patients, the net response was negative. Their over-aerated lung volume decreased by 46 (18-72) mL, but their non-aerated lung volume increased by 107 (44-121) mL., Conclusion: In 20 patients with COVID-19 the net response to decreasing PEEP, as assessed with lung CT, was variable. In approximately half of them it was positive (and possibly beneficial), with a decrease in hyperinflation larger than the increase in collapse., (© 2024 Acta Anaesthesiologica Scandinavica Foundation.)

Micro-computed tomography derived functional biomarkers used in lung disease research can significantly complement end-stage histomorphometric measures while also allowing for longitudinal studies. However, no approach for visualizing lung dynamics across a full respiratory cycle has yet been described. Using bleomycin-induced lung fibrosis and the antifibrotic drug nintedanib as a test model, we implemented a four-dimensional (4D) micro-CT imaging approach consisting of 30 reconstructed volumes per respiratory cycle, coupled with deep-learning-assisted segmentation of lung volumes. 4D micro-CT provided an accurate description of inhalatory and exhalatory lung dynamics under resting conditions and revealed an inflammation-related obstructive pattern at day 7, followed by a restrictive pattern associated with fibrosis development at day 21. A milder restriction and fibrotic pathology resulted from nintedanib treatment. The similarity of 4D micro-CT data with those produced by diagnostic measurements, also points to its great potential as an exploratory tool for the discovery of clinically relevant therapeutic compounds., Competing Interests: F.F.S. and G.V. are employees of Chiesi Farmaceutici S.p.A., that supported the research work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be perceived as a potential conflict of interest., (© 2024 The Author(s).)

Penitentiaries have a higher burden of communicable diseases compared to the general population. Prisoners should be tested for hepatitis C virus (HCV) and have direct access to treatment. We analysed the HCV cascade of care in two penitentiaries in Brescia, Northern Italy. At admission, prisoners are offered a voluntary screening for HCV, while patients with known infections are tested with an HCVRNA measurement. We performed an observational retrospective study including all the subjects admitted to the penitentiaries from 1 January 2015 to 31 October 2021. We conducted a descriptive analysis. During the study period, 5378 admissions were registered, and 2932 (54.5%) screenings were performed. Hepatitis C virus antibody positivity was found in 269 tests (9.2%). Hepatitis C virus RNA was detectable in 169 people. During the study period, 77 treatments with direct-acting antivirals (DAAs) were administered. Follow-up was available in 45 patients, and sustained virological response (SVR) was documented in 44 of them. Retention in care occurred in less than half of the prisoners after release. Our data demonstrate poor screening adherence that could benefit from educational programs. Treatment rates could be improved with test-and-treat programs. More efforts are needed to eliminate HCV as a public threat by 2030. Dedicated local networks, including infectious diseases (ID) departments, substance abuse services and prisons, could mitigate these issues.

The pathogenesis of hypoxemia during acute respiratory distress syndrome caused by SARS-CoV-2 infection (C-ARDS) is debated. Some observations led to hypothesize ventilation to perfusion mismatch, rather than anatomical shunt, as the main determinant of hypoxemia. In this observational study 24 C-ARDS patients were studied 1 (0-1) days after intubation. Patients underwent a CT scan analysis to estimate anatomical shunt and a clinical test to measure venous admixture at two fractions of inspired oxygen (FiO 2 ), to eliminate oxygen-responsive mechanisms of hypoxemia (ventilation to perfusion mismatch and diffusion limitation). In 10 out of 24 patients venous admixture was higher than anatomical shunt both at clinical (≈50 %) and 100 % FiO 2 . These patients were ventilated with a higher PEEP and had lower amount of anatomical shunt compared with patients with venous admixture equal/lower than anatomical shunt. In a subset of C-ARDS patients early after endotracheal intubation, hypoxemia might be explained by an abnormally high perfusion of a relatively low anatomical shunt., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: To develop and validate classifier models that could be used to identify patients with a high percentage of potentially recruitable lung from readily available clinical data and from single CT scan quantitative analysis at intensive care unit admission. 221 retrospectively enrolled mechanically ventilated, sedated and paralyzed patients with acute respiratory distress syndrome (ARDS) underwent a PEEP trial at 5 and 15 cmH 2 O of PEEP and two lung CT scans performed at 5 and 45 cmH 2 O of airway pressure. Lung recruitability was defined at first as percent change in not aerated tissue between 5 and 45 cmH 2 O (radiologically defined; recruiters: Δ 45-5 non-aerated tissue  > 15%) and secondly as change in PaO 2 between 5 and 15 cmH 2 O (gas exchange-defined; recruiters: Δ 15-5 PaO2  > 24 mmHg). Four machine learning (ML) algorithms were evaluated as classifiers of radiologically defined and gas exchange-defined lung recruiters using different models including different variables, separately or combined, of lung mechanics, gas exchange and CT data., Results: ML algorithms based on CT scan data at 5 cmH 2 O classified radiologically defined lung recruiters with similar AUC as ML based on the combination of lung mechanics, gas exchange and CT data. ML algorithm based on CT scan data classified gas exchange-defined lung recruiters with the highest AUC., Conclusions: ML based on a single CT data at 5 cmH 2 O represented an easy-to-apply tool to classify ARDS patients in recruiters and non-recruiters according to both radiologically defined and gas exchange-defined lung recruitment within the first 48 h from the start of mechanical ventilation., (© 2023. The Author(s).)

The outbreak of monkeypox virus (MPXV) in non-endemic countries is an international public health emergency, and the diversity in manifestations poses challenges for early diagnosis and isolation. We describe an atypical case of monkeypox (MPX) in a 46-year-old homosexual male living with HIV. He reported 1-day duration fever, a lesion on his chin that, over a period of 18 days, had gradually enlarged and ulcerated. Biopsy examination performed at an external centre revealed pyoderma gangrenosum, unconfirmed at a subsequent biopsy. When he reported to our hospital outpatients' clinic the chin lesion had a diameter of 5 × 5 cm, necrotic margins and ulcerated base and signs of superinfection. He was admitted for further investigations. Three swabs collected from pharynx, skin and chin lesion resulted positive for MPXV. He had a favourable clinical course and was discharged soon after. Pending the achievement of optimal vaccination coverage in at-risk groups, early identification and isolation of infectious patients represent the cornerstones of the containment strategy. Atypical cases of MPX manifestations are not uncommon, particularly in patients with HIV infection. A high level of suspicion should be maintained to identify infectious cases at an early stage and avoid further spread of the infection., (© 2023. The Author(s).)

Micro-computed tomography (µCT)-based imaging plays a key role in monitoring disease progression and response to candidate drugs in various animal models of human disease, but manual image processing is still highly time-consuming and prone to operator bias. Focusing on an established mouse model of bleomycin (BLM)-induced lung fibrosis we document, here, the ability of a fully automated deep-learning (DL)-based model to improve and speed-up lung segmentation and the precise measurement of morphological and functional biomarkers in both the whole lung and in individual lobes. µCT-DL whose results were overall highly consistent with those of more conventional, especially histological, analyses, allowed to cut down by approximately 45-fold the time required to analyze the entire dataset and to longitudinally follow fibrosis evolution and response to the human-use-approved drug Nintedanib, using both inspiratory and expiratory μCT. Particularly significant advantages of this µCT-DL approach, are: (i) its reduced experimental variability, due to the fact that each animal acts as its own control and the measured, operator bias-free biomarkers can be quantitatively compared across experiments; (ii) its ability to monitor longitudinally the spatial distribution of fibrotic lesions, thus eliminating potential confounding effects associated with the more severe fibrosis observed in the apical region of the left lung and the compensatory effects taking place in the right lung; (iii) the animal sparing afforded by its non-invasive nature and high reliability; and (iv) the fact that it can be integrated into different drug discovery pipelines with a substantial increase in both the speed and robustness of the evaluation of new candidate drugs. The µCT-DL approach thus lends itself as a powerful new tool for the precision preclinical monitoring of BLM-induced lung fibrosis and other disease models as well. Its ease of operation and use of standard imaging instrumentation make it easily transferable to other laboratories and to other experimental settings, including clinical diagnostic applications., (© 2023. The Author(s).)

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in serum immunoglobulins and early-onset infections. Coronavirus Disease-2019 (COVID-19) pneumonia in immunocompromised patients presents clinical and radiological peculiarities which have not yet been completely understood. Very few cases of agammaglobulinemic patients with COVID-19 have been reported since the beginning of the pandemic in February 2020. We report two cases of migrant COVID-19 pneumonia in XLA patients.

Experimental in-vivo animal models are key tools to investigate the pathogenesis of lung disease and to discover new therapeutics. Histopathological and biochemical investigations of explanted lung tissue are currently considered the gold standard, but they provide space-localized information and are not amenable to longitudinal studies in individual animals. Here, we present an imaging procedure that uses micro-CT to extract morpho-functional indicators of lung pathology in a murine model of lung fibrosis. We quantified the decrease of lung ventilation and measured the antifibrotic effect of Nintedanib. A robust structure-function relationship was revealed by cumulative data correlating micro-CT with histomorphometric endpoints. The results highlight the potential of in-vivo micro-CT biomarkers as novel tools to monitor the progression of inflammatory and fibrotic lung disease and to shed light on the mechanism of action of candidate drugs. Our platform is also expected to streamline translation from preclinical studies to human patients., (© 2023. The Author(s).)

Introduction: Young adults with vertical transmission (VT) of human immunodeficiency virus (HIV) represent a fragile population. This study evaluates factors associated with viro-immunological outcome of these patients., Methods: We performed a multicenter study including HIV-infected subjects with VT ≥ 18 years old from six Italian clinics. Subjects were observed from birth to death, lost to follow-up, or last visit until December 31, 2019. Condition of "optimal viro-immunological status" (OS) was defined as the simultaneous presence of HIV ribonucleic acid (RNA) < 50 copies/mL, CD4+ > 500 cells/mm 3 , and CD4+/CD8+ ratio ≥ 1., Results: A total of 126 subjects were enrolled. At 18 years of age, 52/126 (44.4%) had HIV-RNA > 50 copies/mL, 47/126 (38.2%) had CD4+ < 500/mm 3 , and 78/126 (67.2%) had CD4+/CD8+ < 1; 28 subjects (23.7%) presented in the condition of OS. Having a CD4+/CD8+ ratio ≥ 1 at 18 years of age was related with an increased probability of shift from suboptimal viro-immunological status (SOS) to OS (HR: 7.7, 95% confidence interval [CI]: 4.23-14.04), and a reduced risk of shift from the OS to the SOS (HR: 0.49, 95% CI: 0.26-0.92). Acquired immunodeficiency syndrome (AIDS) diagnosis significantly reduced the probability of shift from a viro-immunological SOS to OS (HR: 0.09, 95% CI: 0.03-0.30). Subjects who had not achieved an OS at 18 years of age had an increased risk of discontinuation of combination antiretroviral therapy (cART, p = .019)., Conclusions: Only a small proportion of subjects with VT of HIV reached the adult age with "OS". Transition to the adult care with a compromised viro-immunological condition represents a negative driver for future optimal infection control, with a higher risk of discontinuation of cART and a reduced probability to improve the immunological status later in the years., (© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Electrical impedance tomography (EIT) is a medical imaging technique based on the injection of a current or voltage pattern through electrodes on the skin of the patient, and on the reconstruction of the internal conductivity distribution from the voltages collected by the electrodes. Compared to other imaging techniques, EIT shows significant advantages: it does not use ionizing radiation, is non-invasive and is characterized by high temporal resolution. Moreover, its low cost and high portability make it suitable for real-time, bedside monitoring. However, EIT is also characterized by some technical limitations that cause poor spatial resolution. The possibility to design wearable devices based on EIT has recently given a boost to this technology. In this paper we reviewed EIT physical principles, hardware design and major clinical applications, from the classical to a wearable setup. A wireless and wearable EIT system seems a promising frontier of this technology, as it can both facilitate making clinical measurements and open novel scenarios to EIT systems, such as home monitoring.

Introduction: Fatigue is defined as loss of capacity to develop muscle force and/or velocity that is reversible at rest. We assessed non-invasively the fatigue and recovery of inspiratory rib cage muscles during two respiratory endurance tests in healthy individuals., Methods: The sniff nasal inspiratory pressure (SNIP) was assessed before and after two respiratory endurance tests: normocapnic hyperpnea (NH) and inspiratory pressure threshold loading (IPTL). Contractile (maximum rate of pressure development and time to peak pressure) and relaxation parameters (maximum relaxation rate [MRR], time constant of pressure decay [τ], and half relaxation time) obtained from sniff curves and shortening velocity and mechanical power estimated using optoelectronic plethysmography were analyzed during SNIP maneuvers. Respiratory muscle activity (electromyography) and tissue oxygenation (near-infrared spectroscopy-NIRS) were obtained during endurance tests and SNIP maneuvers. Fatigue development of inspiratory rib cage muscles was assessed according to the slope of decay of median frequency., Results: Peak pressure during SNIP decreased after both protocols (p <0.05). MRR, shortening velocity, and mechanical power decreased (p <0.05), whereas τ increased after IPTL (p <0.05). The median frequency of inspiratory rib cage muscles (i.e., sum of sternocleidomastoid, scalene, and parasternal) decreased linearly during IPTL and exponentially during NH, mainly due to the sternocleidomastoid., Conclusion: Fatigue development behaved differently between protocols and relaxation properties (MRR and τ), shortening velocity, and mechanical power changed only in the IPTL., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Wanderley e Lima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Rationale and Objectives To evaluate associations between longitudinal changes of quantitative CT parameters and spirometry in patients with fibrotic hypersensitivity pneumonitis (HP). Materials and Methods Serial CT images and spirometric data were retrospectively collected in a group of 25 fibrotic HP patients. Quantitative CT analysis included histogram parameters (median, interquartile range, skewness, and kurtosis) and a pretrained convolutional neural network (CNN)-based textural analysis, aimed at quantifying the extent of consolidation (C), fibrosis (F), ground-glass opacity (GGO), low attenuation areas (LAA) and healthy tissue (H). Results At baseline, FVC was 61(44-70) %pred. The median follow-up period was 1.4(0.8-3.2) years, with 3(2-4) visits per patient. Over the study, 8 patients (32%) showed a FVC decline of more than 5%, a significant worsening of all histogram parameters (p≤0.015) and an increased extent of fibrosis via CNN (p=0.038). On histogram analysis, decreased skewness and kurtosis were the parameters most strongly associated with worsened FVC (respectively, r2=0.63 and r2=0.54, p<0.001). On CNN classification, increased extent of fibrosis and consolidation were the measures most strongly correlated with FVC decline (r2=0.54 and r2=0.44, p<0.001). Conclusion CT histogram and CNN measurements provide sensitive measures of functional changes in fibrotic HP patients over time. Increased fibrosis was associated with FVC decline, providing index of disease progression. CNN may help improve fibrotic HP follow-up, providing a sensitive tool for progressive interstitial changes, which can potentially contribute to clinical decisions for individualizing disease management., (Copyright © 2021 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

The development of interstrand-crosslinking (ICL) probes for the covalent targeting of DNA and RNA sequences of interest has been extensively reported in the past decade. However, most of the reactions reported so far induce the formation of a stable adduct that cannot be reverted, thus rendering these chemistries less useful in applications where the reversibility of the reaction is needed for further downstream processing of the targeted and isolated sequences, such as enzymatic amplification steps. In this work, we report on the reversibility of the furan-mediated ICL reaction. ICL formation can be conveniently triggered by either chemical ( N -bromo succinimide, NBS) or luminous stimuli (visible light irradiation in presence of a photosensitizer) and quantitative reversion can be achieved by heating the crosslinked sample at 95 °C, while maintaining the structure of the DNA/RNA targets intact. As a proof-of-concept and showing the benefits of the ICL reversibility, we apply furan-mediated ICL to the pulldown of a target RNA strand from cell lysate., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Prone positioning improves survival in moderate-to-severe acute respiratory distress syndrome (ARDS) unrelated to the novel coronavirus disease (COVID-19). This benefit is probably mediated by a decrease in alveolar collapse and hyperinflation and a more homogeneous distribution of lung aeration, with fewer harms from mechanical ventilation. In this preliminary physiological study we aimed to verify whether prone positioning causes analogue changes in lung aeration in COVID-19. A positive result would support prone positioning even in this other population., Methods: Fifteen mechanically-ventilated patients with COVID-19 underwent a lung computed tomography in the supine and prone position with a constant positive end-expiratory pressure (PEEP) within three days of endotracheal intubation. Using quantitative analysis, we measured the volume of the non-aerated, poorly-aerated, well-aerated, and over-aerated compartments and the gas-to-tissue ratio of the ten vertical levels of the lung. In addition, we expressed the heterogeneity of lung aeration with the standardized median absolute deviation of the ten vertical gas-to-tissue ratios, with lower values indicating less heterogeneity., Results: By the time of the study, PEEP was 12 (10-14) cmH 2 O and the PaO 2 :FiO 2 107 (84-173) mmHg in the supine position. With prone positioning, the volume of the non-aerated compartment decreased by 82 (26-147) ml, of the poorly-aerated compartment increased by 82 (53-174) ml, of the normally-aerated compartment did not significantly change, and of the over-aerated compartment decreased by 28 (11-186) ml. In eight (53%) patients, the volume of the over-aerated compartment decreased more than the volume of the non-aerated compartment. The gas-to-tissue ratio of the ten vertical levels of the lung decreased by 0.34 (0.25-0.49) ml/g per level in the supine position and by 0.03 (- 0.11 to 0.14) ml/g in the prone position (p < 0.001). The standardized median absolute deviation of the gas-to-tissue ratios of those ten levels decreased in all patients, from 0.55 (0.50-0.71) to 0.20 (0.14-0.27) (p < 0.001)., Conclusions: In fifteen patients with COVID-19, prone positioning decreased alveolar collapse, hyperinflation, and homogenized lung aeration. A similar response has been observed in other ARDS, where prone positioning improves outcome. Therefore, our data provide a pathophysiological rationale to support prone positioning even in COVID-19., (© 2022. The Author(s).)

Background: International guidelines suggest using a higher (> 10 cm H 2 O) positive end-expiratory pressure (PEEP) in patients with moderate-to-severe ARDS due to COVID-19. However, even if oxygenation generally improves with a higher PEEP, compliance, and Paco 2 frequently do not, as if recruitment was small., Research Question: Is the potential for lung recruitment small in patients with early ARDS due to COVID-19?, Study Design and Methods: Forty patients with ARDS due to COVID-19 were studied in the supine position within 3 days of endotracheal intubation. They all underwent a PEEP trial, in which oxygenation, compliance, and Paco 2 were measured with 5, 10, and 15 cm H 2 O of PEEP, and all other ventilatory settings unchanged. Twenty underwent a whole-lung static CT scan at 5 and 45 cm H 2 O, and the other 20 at 5 and 15 cm H 2 O of airway pressure. Recruitment and hyperinflation were defined as a decrease in the volume of the non-aerated (density above -100 HU) and an increase in the volume of the over-aerated (density below -900 HU) lung compartments, respectively., Results: From 5 to 15 cm H 2 O, oxygenation improved in 36 (90%) patients but compliance only in 11 (28%) and Paco 2 only in 14 (35%). From 5 to 45 cm H 2 O, recruitment was 351 (161-462) mL and hyperinflation 465 (220-681) mL. From 5 to 15 cm H 2 O, recruitment was 168 (110-202) mL and hyperinflation 121 (63-270) mL. Hyperinflation variably developed in all patients and exceeded recruitment in more than half of them., Interpretation: Patients with early ARDS due to COVID-19, ventilated in the supine position, present with a large potential for lung recruitment. Even so, their compliance and Paco 2 do not generally improve with a higher PEEP, possibly because of hyperinflation., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Introduction: In subjects with obstructive respiratory diseases the increased work of breathing during exercise can trigger greater recruitment and fatigue of respiratory muscles. Associated with these changes, lower limb muscle dysfunctions, further contribute to exercise limitations. We aimed to assess electrical activity and fatigue of two respiratory and one locomotor muscle during Incremental Shuttle Walking Test (ISWT) in individuals with obstructive respiratory diseases and compare with healthy., Methods: This is a case-control study. Seventeen individuals with asthma (asthma group) and fifteen with chronic obstructive pulmonary disease (COPD group) were matched with healthy individuals (asthma and COPD control groups). Surface electromyographic (sEMG) activity of sternocleidomastoid (SCM), scalene (ESC), and rectus femoris (RF) were recorded during ISWT. sEMG activity was analyzed in time and frequency domains at baseline and during the test (33%, 66%, and 100% of ISWT total time) to obtain, respectively, signal amplitude and power spectrum density (EMG median frequency [MF], high- and low-frequency bands, and high/low [H/L] ratio)., Results: Asthma group walked a shorter distance than controls (p = 0.0007). sEMG amplitudes of SCM, ESC, and RF of asthma and COPD groups were higher at 33% and 66% of ISWT compared with controls groups (all p<0.05). SCM and ESC of COPD group remained higher until 100% of the test. MF of ESC and RF decreased in asthma group (p = 0.016 and p < 0.0001, respectively) versus controls, whereas MF of SCM (p < 0.0001) decreased in COPD group compared with controls. H/L ratio of RF decreased (p = 0.002) in COPD group versus controls., Conclusion: Reduced performance is accompanied by increased electromyographic activity of SCM and ESC and activation of RF in individuals with obstructive respiratory diseases during ISWT. These are susceptible to be more pronounced respiratory and peripheral muscle fatigue than healthy subjects during exercise., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Bronchiectasis is a chronic disease characterized by an irreversible dilatation of bronchi leading to chronic infection, airway inflammation, and progressive lung damage. Three specific patterns of bronchiectasis are distinguished in clinical practice: cylindrical, varicose, and cystic. The predominance and the extension of the type of bronchiectasis provide important clinical information. However, characterization is often challenging and is subject to high interobserver variability. The aim of this study is to provide an automatic tool for the detection and classification of bronchiectasis through convolutional neural networks., Materials and Methods: Two distinct approaches were adopted: (i) direct network performing a multilabel classification of 32×32 regions of interest (ROIs) into 4 classes: healthy, cylindrical, cystic, and varicose and (ii) a 2-network serial approach, where the first network performed a binary classification between normal tissue and bronchiectasis and the second one classified the ROIs containing abnormal bronchi into one of the 3 bronchiectasis typologies. Performances of the networks were compared with other architectures presented in the literature., Results: Computed tomography from healthy individuals (n=9, age=47±6, FEV1%pred=109±17, FVC%pred=116±17) and bronchiectasis patients (n=21, age=59±15, FEV1%pred=74±25, FVC%pred=91±22) were collected. A total of 19,059 manually selected ROIs were used for training and testing. The serial approach provided the best results with an accuracy and F1 score average of 0.84, respectively. Slightly lower performances were observed for the direct network (accuracy=0.81 and F1 score average=0.82). On the test set, cylindrical bronchiectasis was the subtype classified with highest accuracy, while most of the misclassifications were related to the varicose pattern, mainly to the cylindrical class., Conclusion: The developed networks accurately detect and classify bronchiectasis disease, allowing to collect quantitative information regarding the radiologic severity and the topographical distribution of bronchiectasis subtype., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Pulmonary lobectomy, which consists of the partial or complete resection of a lung lobe, is the gold standard intervention for lung cancer removal. The removal of functional tissue during the surgery and the re-adaptation of the remaining thoracic structures decrease the patient's post-operative pulmonary function. Residual functionality is evaluated through pulmonary function tests, which account for the number of resected segments without considering local structural alterations and provide an average at-the-mouth estimation. Computational Fluid Dynamics (CFD) has been demonstrated to provide patient-specific, quantitative, and local information about airways airflow dynamics. A CFD investigation was performed on image-based airway trees reconstructed before and after the surgery for twelve patients who underwent lobectomy at different lobes. The geometrical alterations and the variations in fluid dynamics parameters and in lobar ventilation between the pre and post-operative conditions were evaluated. The post-operative function was estimated and compared with current clinical algorithms and with actual clinical data. The post-operative configuration revealed a high intersubject variability: regardless of the lobectomy site, an increment of global velocity, wall pressure, and wall shear stress was observed. Local flow disturbances also emerged at, and downstream of, the resection site. The analysis of lobar ventilation showed severe variations in the volume flow rate distribution, highlighting the compensatory effects in the contralateral lung with an increment of inflow. The estimation of post-operative function through CFD was comparable with the current clinical algorithm and the actual spirometric measurements. The results confirmed that CFD could provide additional information to support the current clinical approaches both in the operability assessment and in the prescription of personalized respiratory rehabilitation., (© 2022. The Author(s).)

Rationale and Objectives: Chronic hypersensitivity pneumonitis (cHP) is a heterogeneous condition, where both small airway involvement and fibrosis may simultaneously occur. Computer-aided analysis of CT lung imaging is increasingly used to improve tissue characterization in interstitial lung diseases (ILD), quantifying disease extension, and progression. We aimed to quantify via a convolutional neural network (CNN) method the extent of different pathological classes in cHP, and to determine their correlation to pulmonary function tests (PFTs) and mosaic attenuation pattern., Materials and Methods: The extension of six textural features, including consolidation (C), ground glass opacity (GGO), fibrosis (F), low attenuation areas (LAA), reticulation (R) and healthy regions (H), was quantified in 27 cHP patients (age: 56 ± 11.5 years, forced vital capacity [FVC]% = 57 ± 17) acquired at full-inspiration via HRCT. Each class extent was correlated to PFTs and to mosaic attenuation pattern., Results: H showed a positive correlation with FVC%, FEV1% (forced expiratory volume), total lung capacity%, and diffusion of carbon monoxide (DLCO)% (r = 0.74, r = 0.78, r = 0.73, and r = 0.60, respectively, p < 0.001). GGO, R and C negatively correlated with FVC% and FEV1% with the highest correlations found for R (r = -0.44, and r = -0.46 respectively, p < 0.05); F negatively correlated with DLCO% (r = -0.42, p < 0.05). Patients with mosaic attenuation pattern had significantly more H (p = 0.04) and lower R (p = 0.02) and C (p = 0.0009) areas, and more preserved lung function indices (higher FVC%; p = 0.04 and DLCO%; p = 0.05), but did not show more air trapping in lung function tests., Conclusion: CNN quantification of pathological tissue extent in cHP improves its characterization and shows correlation with PFTs. LAA can be overestimated by visual, qualitative CT assessment and mosaic attenuation pattern areas in cHP represents patchy ILD rather than small-airways disease., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Micro-computed tomography (micro-CT) imaging is an emerging technology with many applications in small animals, for example, the study of pulmonary diseases, although clear guidelines and critical mass of evidence are still missing in the preclinical literature. The neonatal rabbit is a valuable model for studying pulmonary development. However, the longitudinal monitoring of lung function by micro-CT can be challenging. Distinctive datasets corresponding to the end-inspiration and end-expiration phases need to be generated and analyzed to derive lung-functional parameters. The quality of CT scans and the reliability of parameters obtained remain highly dependent on the anesthesia protocol used. Three different anesthetic protocols were tested. The combination of dexmedetomidine 0.25 mg/kg injected intraperitoneally followed by 1% isoflurane was found to facilitate CT imaging at 4 and 11 days after birth. Contrarily, isoflurane and ketamine-xylazine were found unsuitable and thus not investigated further. Total lung volumes significantly increased at day 11 compared with baseline in both respiratory phases, whereas lung tissue remained constant. As expected, functional residual capacity, air-to-tissue ratio, and minute ventilation were significantly increased at day 11 in each animal. Those parameters were correlated with inspiratory capacity, compliance, elastance, and resistance of both respiratory system and tissue component, as measured by flexiVent. Lung development was also evaluated by histomorphometric analyses. In conclusion, we have identified a safe and suitable anesthesia protocol for micro-CT imaging in neonatal rabbits. Moreover, the possibility to longitudinally measure lung function in the same subject dramatically reduced the intraexperimental variability.

Respiratory muscle weakness is common in neuromuscular disorders (NMDs) and leads to significant respiratory difficulties. Therefore, reliable and easy assessment of respiratory muscle structure and function in NMDs is crucial. In the last decade, ultrasound and magnetic resonance imaging (MRI) have emerged as promising imaging techniques to assess respiratory muscle structure and function. Respiratory muscle imaging directly measures the respiratory muscles and, in contrast to pulmonary function testing, is independent of patient effort. This makes respiratory muscle imaging suitable to use as a tool in clinical respiratory management and as an outcome parameter in upcoming drug trials for NMDs, particularly in children. In this narrative review, we discuss the latest studies and technological developments in imaging of the respiratory muscles by ultrasound and MRI, and its clinical application and limitations. We aim to increase understanding of respiratory muscle imaging and facilitate its use as an outcome measure in daily practice and clinical trials., Competing Interests: Conflict of interest: J.L.M. van Doorn has nothing to disclose. Conflict of interest: F. Pennati has nothing to disclose. Conflict of interest: H.H.G. Hansen has nothing to disclose. Conflict of interest: B.G.M. van Engelen has nothing to disclose. Conflict of interest: A. Aliverti has nothing to disclose. Conflict of interest: J. Doorduin has nothing to disclose., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Computer-aided detection algorithms applied to CT lung imaging have the potential to objectively quantify pulmonary pathology. We aim to develop an automatic classification method based on textural features able to classify healthy and pathological patterns on CT lung images and to quantify the extent of each disease pattern in a group of patients with chronic hypersensitivity pneumonitis (cHP), in comparison to pulmonary function tests (PFTs).27 cHP patients were scanned via high resolution CT (HRCT) at full-inspiration. Regions of interest (ROIs) were extracted and labeled as normal (NOR), ground glass opacity (GGO), reticulation (RET), consolidation (C), honeycombing (HB) and air trapping (AT). For each ROI, statistical, morphological and fractal parameters were computed. For automatic classification, we compared two classification methods (Bayesian and Support Vector Machine) and three ROI sizes. The classifier was therefore applied to the overall CT images and the extent of each class was calculated and compared to PFTs. Better classification accuracy was found for the Bayesian classifier and the 16x16 ROI size: 92.1±2.7%. The extent of GGO, HB and NOR significantly correlated with forced vital capacity (FVC) and the extent of NOR with carbon monoxide diffusing capacity (DLCO).Clinical Relevance- Texture analysis can differentiate and objectively quantify pathological classes in the lung parenchyma and may represent a quantitative diagnostic tool in cHP.

Rationale and Objectives: Acute and chronic graft rejection remains the major problem in clinical surveillance of lung-transplanted patients and early detection of complications is of capital importance to allow the optimal therapeutic option. The aim of this study was to investigate the role of quantitative non contrast-enhanced magnetic resonance imaging (MRI) as a non-ionizing imaging modality to assess ventilation impairment in patients who have undergone lung transplantation, in comparison with quantitative computed tomography (CT) and spirometry., Materials and Methods: Ten lung-transplanted patients (39 ±12 years, forced-expiratory volume in 1 second (FEV1) = 81 ± 27%, forced vital capacity (FVC) = 87 ± 27%) were acquired in breath-hold at full-expiration and full-inspiration with 1.5T MRI and CT. Maps of expiratory-inspiratory difference in MR signal-intensity and CT-density were computed to estimate regional ventilation. Based on expiratory, inspiratory, and expiratory-inspiratory difference values, each pixel was classified as healthy (H), low ventilation (LV), air trapping (AT), and consolidation (C) and the percent extent of each class was quantified., Results: Overall, expiratory-inspiratory difference in MR signal-intensity correlated to CT-density (r = 0.64, p < 0.0001) and to FEV1 (ρ = 0.71, p = 0.02). The linear correlation between MRI and CT functional maps considering all the four classes is r = 0.93 (p < 0.0001). MRI percent volumes of H, AT, and C correlated to FEV1 %pred, with the highest correlation reported for AT (ρ = -0.82)., Conclusion: Results demonstrated a good agreement between MRI and CT ventilation imaging and between the corresponding percent volumes of lung damage. Quantitative MRI may represent an accurate non-ionizing imaging technique for longitudinal monitoring of lung transplant recipients., (Copyright © 2020 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.)

Ventilatory failure, due to the progressive wasting of respiratory muscles, is the main cause of death in patients with Duchenne muscular dystrophy (DMD). Reliable measures of lung function and respiratory muscle action are important to monitor disease progression, to identify early signs of ventilatory insufficiency and to plan individual respiratory management. Moreover, the current development of novel gene-modifying and pharmacological therapies highlighted the urgent need of respiratory outcomes to quantify the effects of these therapies. Pulmonary function tests represent the standard of care for lung function evaluation in DMD, but provide a global evaluation of respiratory involvement, which results from the interaction between different respiratory muscles. Currently, research studies have focused on finding novel outcome measures able to describe the behavior of individual respiratory muscles. This review overviews the measures currently identified in clinical research to follow the progressive respiratory decline in patients with DMD, from a global assessment to an individual structure-function muscle characterization. We aim to discuss their strengths and limitations, in relation to their current development and suitability as outcome measures for use in a clinical setting and as in upcoming drug trials in DMD.

Background: We investigated the influence of diaphragmatic activation control (diaphC) on the relaxation rate, contractile properties and electrical activity of the inspiratory muscles of healthy subjects. Assessments were performed non-invasively using the sniff inspiratory pressure test (SNIP) and surface electromyography, respectively., Methods: Twenty-two subjects (10 men and 12 women) performed 10 sniff maneuvers in two different days: with and without diaphC instructions. For the SNIP test with diaphC, the subjects were instructed to perform intense activation of the diaphragm. The tests with the best SNIP values were used for analysis., Results: The maneuver with diaphC when compared to the maneuver without diaphC exhibited significant lower values for: SNIP (p <0.01), maximum relaxation rate (MRR) (p <0.01), maximum rate of pressure development (MRPD) (p <0.01), contraction times (CT) (p = 0.02) and electrical activity of the sternocleidomastoid (SCM) (p <0.01), scalene (SCL) (p = 0.01) and intercostal (CI) (p = 0.03) muscles. In addition, the decay constant (tau, τ) and relaxation time (½ RT) did not present any changes., Conclusion: The diaphragmatic control performed during the SNIP test influences the inspiratory pressure and the contractile properties of inspiratory muscles. This occurs due to changes in the pattern of muscle recruitment, which change force velocity characteristics of the test. Thus, instruction on diaphC should be encouraged for better performance of the SNIP test and for evaluation targeting the diaphragm muscle activity., Competing Interests: The authors have declared that no competing interests exist.

Objective: To assess thoracoabdominal asynchrony (TAA) and inspiratory paradoxical motion at different positionings in subjects with Duchenne muscular dystrophy (DMD) versus healthy subjects during quiet spontaneous breathing (QB) and cough., Methods: This is a case control study with a matched-pair design. We assessed 14 DMD subjects and 12 controls using optoelectronic plethysmography (OEP) during QB and spontaneous cough in 3 positions: supine, supine with headrest raised at 45°, and sitting with back support at 80°. The TAA was assessed using phase angle (θ) between upper (RCp) and lower rib cage (RCa) and abdomen (AB), as well as the percentage of inspiratory time the RCp (IP RCp ), RCa (IP RCa ), and AB (IP AB ) moved in opposite directions., Results: During cough, DMD group showed higher RCp and RCa θ (p < .05), RCp and AB θ (p < .05) in supine and 45° positions, and higher RCp and Rca θ (p = .006) only in supine position compared with controls. Regarding the intragroup analysis, during cough, DMD group presented higher RCp and AB θ (p = .02) and RCa and AB θ (p = .002) in supine and higher RCa and AB θ (p = .002) in 45° position when compared to 80°. Receiver operating characteristic curve analyzes were able to discriminate TAA between controls and DMD in RCa supine position (area under the curve: 0.81, sensibility: 78.6% and specificity: 91.7%, p = .001)., Conclusion: Subjects with DMD yields TAA with insufficient deflation of chest wall compartments and rib cage distortion during cough, by noninvasive assessment., (© 2021 Wiley Periodicals LLC.)

Pulmonary lobectomy is the gold standard intervention for lung cancer removal and consists of the complete resection of the affected lung lobe, which, coupled with the re-adaptation of the remaining thoracic structures, decreases the postoperative pulmonary function of the patient. Current clinical practice, based on spirometry and cardiopulmonary exercise tests, does not consider local changes, providing an average at-the-mouth estimation of residual functionality. Computational Fluid Dynamics (CFD) has proved a valuable solution to obtain quantitative and local information about airways airflow dynamics. A CFD investigation was performed on the airway tree of a left-upper pulmonary lobectomy patient, to quantify the effects of the postoperative alterations. The patient-specific bronchial models were reconstructed from pre- and postoperative CT scans. A parametric laryngeal model was merged to the geometries to account for physiological-like inlet conditions. Numerical simulations were performed in Fluent. The postoperative configuration revealed fluid dynamic variations in terms of global velocity (+23%), wall pressure (+48%), and wall shear stress (+39%). Local flow disturbances emerged at the resection site: a high-velocity peak of 4.92 m/s was found at the left-lower lobe entrance, with a local increase of pressure at the suture zone (18 Pa). The magnitude of pressure and secondary flows increased in the trachea and flow dynamics variations were observed also in the contralateral lung, causing altered lobar ventilation. The results confirmed that CFD is a patient-specific approach for a quantitative evaluation of fluid dynamics parameters and local ventilation providing additional information with respect to current clinical approaches., (© 2021 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.)

Muscle fatigue is a complex phenomenon enclosing various mechanisms. Despite technological advances, these mechanisms are still not fully understood in vivo. Here, simultaneous measurements of pressure, volume, and ribcage inspiratory muscle activity were performed non-invasively during fatigue (inspiratory threshold valve set at 70% of maximal inspiratory pressure) and recovery to verify if inspiratory ribcage muscle fatigue (1) leads to slowing of contraction and relaxation properties of ribcage muscles and (2) alters median frequency and high-to-low frequency ratio (H/L). During the fatigue protocol, sternocleidomastoid showed the fastest decrease in median frequency and slowest decrease in H/L. Fatigue was also characterized by a reduction in the relative power of the high-frequency and increase of the low-frequency. During recovery, changes in mechanical power were due to changes in shortening velocity with long-lasting reduction in pressure generation, and slowing of relaxation [i.e., tau (τ), half-relaxation time (½RT), and maximum relaxation rate (MRR)] was observed with no significant changes in contractile properties. Recovery of median frequency was faster than H/L, and relaxation rates correlated with shortening velocity and mechanical power of inspiratory ribcage muscles; however, with different time courses. Time constant of the inspiratory ribcage muscles during fatigue and recovery is not uniform (i.e., different inspiratory muscles may have different underlying mechanisms of fatigue), and MRR, ½RT, and τ are not only useful predictors of inspiratory ribcage muscle recovery but may also share common underlying mechanisms with shortening velocity.

Background: MRI has been suggested as a radiation-free imaging modality to investigate early structural alterations and regional functional impairment in cystic fibrosis (CF) lung disease., Purpose/hypothesis: To compare functional and morphological MRI changes over the course of the disease to changes in spirometry., Study Type: Longitudinal retrospective study., Population: Twenty patients with CF lung disease (at baseline, age = 16.5 (13.3-20.6) years, forced expiratory volume in 1 second (as % of predicted [%pred]) FEV 1 = 71 (59-87) %pred, forced expiratory flow at 25-75% of forced vital capacity FEF 25-75 = 39 (25-63) %pred., Field Strength/sequence: 1.5T / T 2 -weighted HASTE; T 2 -weighted TSE-PROPELLER; T 2 -weighted bSSFP; T 1 -weighted 3D GRE., Assessment: Nonenhanced chest MRI and spirometry were retrospectively collected over a 3-year period from the initial recruitment visit. Images acquired at end-inspiration and end-expiration were registered by software using the optical flow method to measure expiratory-inspiratory differences in MR signal-intensity (Δ 1 H-MRI). Measures of CF functional impairment were defined from Δ 1 H-MRI: Δ 1 H-MRI median, Δ 1 H-MRI quartile coefficient of variation (QCV), and percent low-signal-variation volume (LVV). MR images were also evaluated by three readers using a CF-specific scoring system., Statistical Tests: Spearman correlation analysis, Spearman rank correlation analysis, linear mixed-effect model analysis, intraclass correlation coefficient., Results: Functional imaging parameters and total morphological score correlated with all spirometric measures, as did subscores of bronchial wall thickening/bronchiectasis, mucus plugging, and consolidation. Overall, the percent change of Δ1H-MRI median correlated with the percent change of FEV 1 (ΔFEV 1 , r = 0.41, P < 0.01) and the percent change of FEF 25-75 (ΔFEF25-75%, r = 0.38, P < 0.01). The percent change of LVV correlated with ΔFEV 1 (r = -0.47, P < 0.001) and ΔFEF 25-75 (r = -0.50, P < 0.001)., Data Conclusion: These preliminary results suggest that nonenhanced multivolume MRI may provide a feasible tool to regionally map early pulmonary alterations for longitudinal evaluation of CF lung disease, without exposing the patients to ionizing radiation., Level of Evidence: 3T TECHNICAL EFFICACY STAGE: 5., (© 2020 International Society for Magnetic Resonance in Medicine.)

Pulmonary complications following allogeneic hematopoietic stem-cell transplantation (HSCT) are a significant source of morbidity and complications may arise from a myriad of infectious and noninfectious sources. These complications may occur soon or many months post-transplantation and can have a broad range of outcomes. Surveillance for pulmonary involvement in the pediatric HSCT population can be challenging due to poor compliance with clinical pulmonary function testing, primarily spirometry, and there may be a role for clinical imaging to provide an additional means of monitoring, particularly in the era of clinical low-dose computed tomography (CT) protocols. In this single-site, retrospective study, a review of our institution's radiological and HSCT databases was conducted to assess the utility of a quantitative CT algorithm to describe ventilation abnormalities on high-resolution chest CT scans of pediatric HSCT patients. Thirteen non-contrast enhanced chest CT examinations acquired both in inspiration and expiration, from 12 deceased HSCT patients (median age at HSCT 10.4 years, median days of CT 162) were selected for the analysis. Also, seven age-matched healthy controls (median age 15.5) with non-contrast-enhanced inspiration-expiration chest CT were selected for comparison. We report that, compared to healthy age-matched controls, HSCT patients had larger percentages of poorly ventilated (median, 13.5% vs. 2.3%, p < .001) and air trapped (median 12.3% vs. 0%, p < .001) regions of lung tissue, suggesting its utility as a potential screening tool. Furthermore, there was wide variation within individual HSCT patients, supporting the use of multivolume CT and quantitative analysis to describe and phenotype post-transplantation lung involvement., (© 2020 Wiley Periodicals LLC.)

During the SARS-CoV-2 pandemic, the province of Brescia (Italy) had a significant number of COVID-19 cases, which led to a subversion of the ordinary structure of the university hospital ASST Spedali Civili, driven by the need to hospitalize as many patients as possible in a narrow period of time. At the peak of the epidemic, a rapid hospitalization discharge area, the Discharge Ward (DW), was set up with the aim of facilitating the rapid turnover of patients in the wards where the most severe patients had to be hospitalized. The organization and activities carried out are described in the results of this reproducible experience during epidemic events.