Airway Remodeling in Cystic Fibrosis Is Heterogeneous.

RATIONALE+OBJECTIVE/ Cystic fibrosis (CF) is characterized by bronchiectasis on imaging, while functionally evolving towards obstructive impairment. Despite its assumed importance in CF, small airway remodeling and its relation to bronchiectasis, is still poorly understood. METHOD/ On high-resolution computed tomography (HRCT, 600µm, CF=21, control=6) and micro-computed tomography (µCT, 150µm, CF=3, control=1) scans of inflated explant lungs, AV% (airway/total lung volume) was calculated as marker for bronchiectasis, while airway segmentation was used for generation analysis.

Respiratory muscle dysfunction in acute and chronic respiratory failure: how to diagnose and how to treat?

Assessing and treating respiratory muscle dysfunction is crucial for patients with both acute and chronic respiratory failure. Respiratory muscle dysfunction can contribute to the onset of respiratory failure and may also worsen due to interventions aimed at treatment. Evaluating respiratory muscle function is particularly valuable for diagnosing, phenotyping and assessing treatment efficacy in these patients.

Histological analysis of the medial gastrocnemius muscle in young healthy children.

Histological data on muscle fiber size and proportion in (very) young typically developing (TD) children is not well documented and data on capillarization and satellite cell content are also lacking. This study investigated the microscopic properties of the medial gastrocnemius muscle in growing TD children, grouped according to age and gender to provide normal reference values in healthy children. Microbiopsies of the medial gastrocnemius (MG) muscle were collected in 46 TD boys and girls aged 2-10 years subdivided into 4 age groups (2-4, 4-6, 6-8 and 8-10 years).

Smoking cessation only partially reverses cardiac metabolic and structural remodeling in mice.

Aims: Active cigarette smoking is a major risk factor for chronic obstructive pulmonary disease that remains elevated after cessation. Skeletal muscle dysfunction has been well documented after smoking, but little is known about cardiac adaptations to cigarette smoking. The underlying cellular and molecular cardiac adaptations, independent of confounding lifestyle factors, and time course of reversibility by smoking cessation remain unclear.

Short-Term Effects of Botulinum Toxin-A Injection on the Medial Gastrocnemius Histological Features in Ambulant Children with Cerebral Palsy: A Longitudinal Pilot Study.

Botulinum toxin-A (BoNT-A) injection is known to exert beneficial effects on muscle tone, joint mobility and gait in children with cerebral palsy (CP). However, recent animal and human studies have raised the concern that BoNT-A might be harmful to muscle integrity. In CP-children, the impact of BoNT-A on muscle structure has been poorly studied, and inconsistent results have been reported.

Histological analysis of the gastrocnemius muscle in preschool and school age children with cerebral palsy compared with age-matched typically developing children.

Inconsistent alterations in skeletal muscle histology have been reported in adolescents with cerebral palsy (CP) and whether alterations are present in young children and differ from older children is not yet known. This study aimed to define histological alterations in the medial gastrocnemius (MG) of ambulant CP (gross-motor classification system, GMFCS I-III) stratified in two age groups (preschool children, PS: 2-5 and school age children, SA: 6-9-yr old) compared with age-matched typically developing (TD) children. We hypothesized that alterations in muscle microscopic properties are already present in PS-CP and are GMFCS level specific.

Fine-needle percutaneous muscle microbiopsy technique as a feasible tool to address histological analysis in young children with cerebral palsy and age-matched typically developing children.

Cerebral palsy (CP) is a heterogeneous group of motor disorders attributed to a non-progressive lesion in the developing brain. Knowledge on skeletal muscle properties is important to understand the impact of CP and treatment but data at the microscopic levels are limited and inconsistent. Currently, muscle biopsies are collected during surgery and are restricted to CP eligible for such treatment or they may refer to another muscle or older children in typically developing (TD) biopsies.

Mucosal immune alterations at the early onset of tissue destruction in chronic obstructive pulmonary disease.

Rationale: COPD is characterized by chronic airway inflammation, small airways changes, with disappearance and obstruction, and also distal/alveolar destruction (emphysema). The chronology by which these three features evolve with altered mucosal immunity remains elusive. This study assessed the mucosal immune defense in human control and end-stage COPD lungs, by detailed microCT and RNA transcriptomic analysis of diversely affected zones.

Effects of inspiratory muscle training on exertional breathlessness in patients with unilateral diaphragm dysfunction: a randomised trial.

Background: Unilateral diaphragm dysfunction (UDD) is an underdiagnosed cause of dyspnoea. Inspiratory muscle training (IMT) is the only conservative treatment for UDD, but the mechanisms of improvement are unknown. We characterised the effects of IMT on dyspnoea, exercise tolerance and respiratory muscle function in people with UDD.

Botulinum Toxin Treatment of Adult Muscle Stem Cells from Children with Cerebral Palsy and hiPSC-Derived Neuromuscular Junctions.

Botulinum neurotoxin type-A (BoNT) injections are commonly used as spasticity treatment in cerebral palsy (CP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised, and the BoNT effect on muscle stem cells remains not well defined. This study aims at clarifying the impact of BoNT on growing muscles (1) by analyzing the in vitro effect of BoNT on satellite cell (SC)-derived myoblasts and fibroblasts obtained from medial gastrocnemius microbiopsies collected in young BoNT-naïve children (t0) compared to age ranged typically developing children; (2) by following the effect of in vivo BoNT administration on these cells obtained from the same children with CP at 3 (t1) and 6 (t2) months post BoNT; (3) by determining the direct effect of a single and repeated in vitro BoNT treatment on neuromuscular junctions (NMJs) differentiated from hiPSCs.

COVID-19 progression in hospitalized patients using follow-up CT and microCT.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease-19 (COVID-19) which can lead to acute respiratory distress syndrome (ARDS) and evolve to pulmonary fibrosis. Computed tomography (CT) is used to study disease progression and describe radiological patterns in COVID-19 patients. This study aimed to assess disease progression regarding lung volume and density over time on follow-up chest CT and give a unique look at parenchymal and morphological airway changes in "end-stage" COVID-19 lungs using microCT.

A Nrf2-OSGIN1&2-HSP70 axis mediates cigarette smoke-induced endothelial detachment: implications for plaque erosion.

Aims: Endothelial erosion of plaques is responsible for ∼30% of acute coronary syndromes (ACS). Smoking is a risk factor for plaque erosion, which most frequently occurs on the upstream surface of plaques where the endothelium experiences elevated shear stress. We sought to recreate these conditions in vitro to identify potential pathological mechanisms that might be of relevance to plaque erosion.

Local nebulization of 1α,25(OH)D attenuates LPS-induced acute lung inflammation.

Background: Evidence supports a critical role of vitamin D status on exacerbation in chronic obstructive pulmonary disease, indicating the need to avoid vitamin D deficiency in these patients. However, oral vitamin D supplementation is limited by the potential risk for hypercalcemia. In this study, we investigated if local delivery of vitamin D to the lungs improves vitamin D-mediated anti-inflammatory action in response to acute inflammation without inducing hypercalcemia.

Effects of repeated infections with non-typeable Haemophilus influenzae on lung in vitamin D deficient and smoking mice.

Background: In chronic obstructive pulmonary disease (COPD), exacerbations cause acute inflammatory flare-ups and increase the risk for hospitalization and mortality. Exacerbations are common in all disease stages and are often caused by bacterial infections e.g.

Reduced Cross-Sectional Muscle Growth Six Months after Botulinum Toxin Type-A Injection in Children with Spastic Cerebral Palsy.

Botulinum Neurotoxin type-A (BoNT-A) injections are widely used as first-line spasticity treatment in spastic cerebral palsy (SCP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised. Yet, the risk of initiating BoNT-A to reduce muscle growth remains unclear.

Vitamin D Actions: The Lung Is a Major Target for Vitamin D, FGF23, and Klotho.

Vitamin D is well known for its role as a calcium regulator and in maintenance of phosphate homeostasis in musculoskeletal health, and fibroblast growth factor 23 (FGF23) and its coreceptor α-klotho are known for their roles as regulators of serum phosphate levels. However, apart from these classical actions, recent data point out a relevant role of vitamin D and FGF23/klotho in lung health. The expression of the vitamin D receptor by different cell types in the lung and the fact that those cells respond to vitamin D or can locally produce vitamin D indicate that the lung represents a target for vitamin D actions.

The combination of smoking with vitamin D deficiency impairs skeletal muscle fiber hypertrophy in response to overload in mice.

Vitamin D deficiency, which is highly prevalent in the general population, exerts similar deleterious effects on skeletal muscles to those induced by cigarette smoking. We examined whether cigarette smoke (CS) exposure and/or vitamin D deficiency impairs the skeletal muscle hypertrophic response to overload. Male C57Bl/6JolaH mice on a normal or vitamin D-deficient diet were exposed to CS or room air for 18 wk.

Enhanced lung inflammatory response in whole-body compared to nose-only cigarette smoke-exposed mice.

Background: Chronic obstructive pulmonary disease (COPD) is characterized by a progressive and abnormal inflammatory response in the lungs, mainly caused by cigarette smoking. Animal models exposed to cigarette smoke (CS) are used to mimic human COPD but the use of different CS protocols makes it difficult to compare the immunological and structural consequences of using a nose-only or whole-body CS exposure system. We hypothesized that when using a standardized CS exposure protocol based on particle density and CO (carbon monoxide) levels, the whole-body CS exposure system would generate a more severe inflammatory response than the nose-only system, due to possible sensitization by uptake of CS-components through the skin or via grooming.

Muscle Microbiopsy to Delineate Stem Cell Involvement in Young Patients: A Novel Approach for Children With Cerebral Palsy.

Cerebral palsy (CP), the single largest cause of childhood physical disability, is characterized firstly by a lesion in the immature brain, and secondly by musculoskeletal problems that progress with age. Previous research reported altered muscle properties, such as reduced volume and satellite cell (SC) numbers and hypertrophic extracellular matrix compared to typically developing (TD) children (>10 years). Unfortunately, data on younger CP patients are scarce and studies on SCs and other muscle stem cells in CP are insufficient or lacking.

Local expression profiles of vitamin D-related genes in airways of COPD patients.

Treatment of Chronic Obstructive Pulmonary Disease (COPD) is based on bronchodilation, with inhaled corticosteroids or azithromycin associated when frequent exacerbations occur. Despite the proven benefits of current treatment regimens, the need for new interventions in delineated subgroups remains. There is convincing evidence for oral vitamin D supplementation in reducing exacerbations in COPD patients severely deficient for circulating vitamin D.

Pathological Comparisons of Paraseptal and Centrilobular Emphysema in Chronic Obstructive Pulmonary Disease.

Although centrilobular emphysema (CLE) and paraseptal emphysema (PSE) are commonly identified on multidetector computed tomography (MDCT), little is known about the pathology associated with PSE compared with that of CLE. To assess the pathological differences between PSE and CLE in chronic obstructive pulmonary disease (COPD). Air-inflated frozen lung specimens ( = 6) obtained from patients with severe COPD treated by lung transplantation were scanned with MDCT.

Effects of downhill walking in pulmonary rehabilitation for patients with COPD: a randomised controlled trial.

The development of contractile muscle fatigue (CMF) affects training responses in patients with chronic obstructive pulmonary disease (COPD). Downhill walking induces CMF with lower dyspnoea and fatigue than level walking. This study compared the effect of pulmonary rehabilitation (PR) comprising downhill walking training (DT) to PR comprising level walking (conventional training (CT)) in patients with COPD.

Copper-Heparin Inhalation Therapy To Repair Emphysema: A Scientific Rationale.

Current pharmacotherapy of chronic obstructive pulmonary disease (COPD) aims at reducing respiratory symptoms and exacerbation frequency. Effective therapies to reduce disease progression, however, are still lacking. Furthermore, COPD medications showed less favorable effects in emphysema than in other COPD phenotypes.