Changes In Lung Structure Research Articles

Inflamacija disajnih puteva kod pacijenata sa bronhiektazijama

Bronchiectasis is a chronic lung disease characterized by an abnormal dilation of the bronchial lumen caused by weakening or destruction of the muscle or elastic components of the bronchial wall, decreased mucous clearance and frequent infections of the respiratory tract. The golden standard for bronchiectasis diagnosis is high-resolution computed tomography (HRCT) of the chest. Inflammation holds a central role in the development of structural lung changes, as well as airway and lung parenchyma damage. Infection and colonization of the respiratory tract contribute to increased inflammation and further damage to the lung. Upon entry into the respiratory tract, the pathogens activate epithelial cells, macrophages and dendritic cells. Activated inflammatory cells secrete chemical mediators which activate the immune response and thus allow the phagocytosis of pathogens. Early diagnosis, appropriate treatment and interruption of the vicious circle between infection and inflammation in patients suffering from bronchiectasis, prevent the development of structural changes to the airways.

Asthma with Irreversible Airway Obstruction in Smokers and Nonsmokers: Links between Airway Inflammation and Structural Changes

Background: The development of irreversible airway obstruction (IRAO) in asthma is related to lung/airway inflammatory and structural changes whose characteristics are likely influenced by exposure to tobacco smoke. Objective: To investigate the interplay between airway and lung structural changes, airway inflammation, and smoking exposure in asthmatics with IRAO. Methods: We studied asthmatics with IRAO who were further classified according to their smoking history, those with ≥20 pack-years of tobacco exposure (asthmatics with smoking-related IRAO [AwS-IRAO]) and those with <5 pack-years of tobacco exposure (asthmatics with nonsmoking-related IRAO [AwNS-IRAO]). In addition to recording baseline clinical and lung function features, all patients had a chest computed tomography (CT) from which airway wall thickness was measured and quantitative and qualitative assessment of emphysema was performed. The airway inflammatory profile was documented from differential inflammatory cell counts on induced sputum. Results: Ninety patients were recruited (57 AwS-IRAO and 33 AwNS-IRAO). There were no statistically significant differences in the extent of emphysema and gas trapping between groups on quantitative chest CT analysis, although Pi10, a marker of airway wall thickness, was significantly higher in AwS-IRAO (p = 0.0242). Visual analysis showed a higher prevalence of emphysema (p = 0.0001) and higher emphysema score (p < 0.0001) in AwS-IRAO compared to AwNS-IRAO and distribution of emphysema was different between groups. Correlations between radiological features and lung function were stronger in AwS-IRAO. In a subgroup analysis, we found a correlation between airway neutrophilia and emphysematous features in AwS-IRAO and between eosinophilia and both airway wall thickness and emphysematous changes in AwNS-IRAO. Conclusions: Although bronchial structural changes were relatively similar in smoking and nonsmoking patients with asthma and IRAO, emphysematous changes were more predominant in smokers. However, neutrophils in AwS-IRAO and eosinophils in AwNS-IRAO were associated with lung and airway structural changes.

Chronic cigarette smoke exposure and pneumococcal infection induce oropharyngeal microbiota dysbiosis and contribute to long-lasting lung damage in mice.

Environmental factors, such as cigarette smoking or lung infections, may influence chronic obstructive pulmonary disease (COPD) progression by modifying the respiratory tract microbiome. However, whether the disease itself induces or maintains dysbiosis remains undefined. In this longitudinal study, we investigated the oropharyngeal microbiota composition and disease progression of mice (in cages of 5–10 mice per cage) before, during and up to 3 months after chronic cigarette smoke exposure or exposure to room air for 6 months. Cigarette smoke exposure induced pulmonary emphysema measurable at the end of exposure for 6 months, as well as 3 months following smoke exposure cessation. Using both classical culture methods and 16S rRNA sequencing, we observed that cigarette smoke exposure altered the relative composition of the oropharyngeal microbiota and reduced its diversity (P <0.001). More than 60 taxa were substantially reduced after 6 months of smoke exposure (P <0.001) However, oropharyngeal microbiota disordering was reversed 3 months after smoke exposure cessation and no significant difference was observed compared to age-matched control mice. The effects of lung infection with Streptococcus pneumoniae on established smoke-induced emphysema and on the oropharyngeal microbiota were also evaluated. Inoculation with S. pneumoniae induced lung damage and altered the microbiota composition for a longer time compared to control groups infected but not previously exposed to smoke (P=0.01). Our data demonstrate effects of cigarette smoke and pneumococcus infection leading to altered microbiota and emphysema development. The reversal of the disordering of the microbiota composition, but not lung damage, following smoke exposure cessation and after clearance of infection suggest that changes in lung structure are not sufficient to sustain a disordered microbiota in mice. Whether changes in the airway microbiota contribute to inducing emphysema requires further investigation.

High incidence and mortality of pneumothorax in critically Ill patients with COVID-19

BackgroundThe clinical characteristics of the patients with COVID-19 complicated by pneumothorax have not been clarified. ObjectivesTo determine the epidemiology and risks of pneumothorax in the critically ill patients with COVID-19. MethodsRetrospectively collecting and analysing medical records, laboratory findings, chest X-ray and CT images of 5 patients complicated by pneumothorax. ResultsThe incidence of pneumothorax was 10% (5/49) in patients with ARDS, 24% (5/21) in patients receiving mechanical ventilation, and 56% (5/9) in patients requiring invasive mechanical ventilation, with 80% (4/5) patients died. All the 5 patients were male and aged ranging from 54 to 79 years old. Pneumothorax was most likely to occur 2 weeks after the beginning of dyspnea and associated with reduction of neuromuscular blockers, recruitment maneuver, severe cough, changes of lung structure and function. ConclusionsPneumothorax is a frequent and fatal complication of critically ill patients with COVID-19.

Decreased AMP-activated protein kinase (AMPK) function and protective effect of metformin in neonatal rat pups exposed to hyperoxia lung injury.

We investigated the hypothesis that exposure of lungs at the saccular stage of development to hyperoxia leads to persistent growth arrest and dysfunction of 5’AMP‐activated protein kinase (AMPK), a key energy sensor in the cell. We exposed neonatal rat pups from postnatal day 1‐ day 10 (P1–P10) to ≥90% oxygen or control normoxia. Pups were euthanized at P4 or P10 or recovered in normoxia until euthanasia at P21. Half of the pups in each group received AMPK activator, metformin, or saline intraperitoneally from P1 to P10. Lung histology, morphometric analysis, immunofluorescence, and immunoblots were done for changes in lung structure at P10 and P21 and AMPK function at P4, P10, and P21. Phosphorylation of AMPK (p‐AMPK) was decreased in lungs at P10 and P21 in hyperoxia‐exposed pups. Metformin increased the levels of p‐AMPK and PGC‐1α, a downstream AMPK target which regulates mitochondrial biogenesis, at P4, P10, and P21 in hyperoxia pups. Lung ATP levels decreased during hyperoxia and were increased by metformin at P10 and P21. Radial alveolar count and alveolar septal tips were decreased and mean linear intercept increased in hyperoxia‐exposed pups at P10 and the changes persisted at P21; these were improved by metformin. Lung capillary number was decreased in hyperoxia‐exposed pups at P10 and P21 and was restored by metformin. Hyperoxia leads to impaired AMPK function, energy balance and alveolar simplification. The AMPK activator, metformin improves AMPK function and alveolar and vascular growth in this rat pup model of hyperoxia‐induced lung injury.

Magnetic resonance imaging of the lungs in cystic fibrosis

Disease severity and mortality in patients with cystic fibrosis (CF) is mainly determined by (progressive) pulmonary lung disease. Early diagnosis and therapy are important and of prognostic value to conserve lung function. Primary imaging techniques for lung imaging are x‑ray and computed tomography (CT) to monitor disease severity and regional distribution. Radiation-free imaging techniques such as magnetic resonance imaging (MRI) have gained interest over the last decade in order to prevent radiation damage. The main findings of CF lung disease are airway wall thickening, bronchiectasis, and mucus plugging, which are found in up to 60% of preschool age children. Pleural abnormalities and consolidations are often associated with pulmonary exacerbation. Young CF patients often show amosaic pattern as functional changes and also perfusion defects can be seen from birth in 50% of CF patients by contrast-enhanced perfusion imaging, and in up to 90% of adult patients, with varying degrees of severity. Dilated bronchial arteries indicate an increased risk for hemoptysis. Proton MRI is the sole imaging technique that can show structural and functional lung changes in one examination. Structured assessment using ascoring system helps to systematically grade the extent and severity of all CF-associated changes. Lung MRI for cystic fibrosis has been recently established as aclinical standard examination and is routinely performed at experienced centers. More recently, it has also been used as an endpoint within the framework of clinical studies.

Parallel epidemics, or nearly so: Certainties and uncertainties about SARS-CoV-2 in Italy

Parallel epidemics, or nearly so: Certainties and uncertainties about SARS-CoV-2 in Italy

Mesenchymal folliculin is required for alveolar development: implications for cystic lung disease in Birt-Hogg-Dubé syndrome

BackgroundPulmonary cysts and spontaneous pneumothorax are presented in most patients with Birt-Hogg-Dubé (BHD) syndrome, which is caused by loss of function mutations in the folliculin (FLCN) gene. The pathogenic mechanisms...

Postnatal Changes of Lung Structure in Albino Rats after Aluminum Chloride Exposure and Possible Protective Role of Omega 3

Postnatal Changes of Lung Structure in Albino Rats after Aluminum Chloride Exposure and Possible Protective Role of Omega 3

Longitudinal changes in structural lung abnormalities using MDCT in chronic obstructive pulmonary disease with asthma-like features.

Some patients with chronic obstructive pulmonary disease (COPD) have asthma-like features. However, there have been few reports on the structural lung abnormalities found in this patient population. Multi-detector computed tomography (MDCT) can detect emphysematous low-attenuation areas (LAA) within the lung, airway thickness (wall area percentage, WA%), and the loss of pulmonary vasculature as the percentage of small pulmonary vessels with cross-sectional area (CSA) less than 5 mm2 (%CSA<5). We analyzed differences in structural lung changes over time between patients with COPD and those with COPD with asthma-like features using these CT parameters. We performed pulmonary function tests (PFTs), MDCT, and a COPD assessment test (CAT) in 50 patients with COPD and 29 patients with COPD with asthma-like features at the time of enrollment and two years later. We analyzed changes in clinical parameters and CT indices over time and evaluated differences in structural changes between groups. The CAT score and FEV1 did not significantly change during the follow-up period in either group. Emphysematous LAA regions significantly increased in both groups. The %CSA<5 showed a small but significant increase in COPD patients, but a significant decrease in patients with COPD with asthma-like features. The WA% at the distal bronchi was significantly decreased in COPD, but did not significantly change in COPD with asthma -like features. Emphysematous LAA increased in patients with COPD with and without asthma-like features. The %CSA<5 and WA% at the distal bronchi did not change in parallel with LAA. Furthermore, changes in %CSA<5 were significantly different between patients with COPD and those with COPD with asthma-like features. Patients with COPD with asthma-like features may have different longitudinal structural changes than those seen in COPD patients.

Bronchiectasis in PCD looks different to CF on CT scan

Background: The contemporary diagnosis of bronchiectasis requires CT scanning to describe specific structural lung changes. Scoring systems have been designed and validated in some specific causes of bronchiectasis to allow investigators to correlate CT changes with other indices of disease severity, to describe changes over time, with exacerbation and in response to treatment. Several scoring systems have been developed for CF including the Bhalla Score, Brody score, and the Helbich score. These scoring systems have also been applied to other causes of bronchiectasis including Primary Ciliary Dyskinesia (PCD). This assumes that the nature of structural lung disease in these conditions, as well as the rate and nature of longitudinal changes are identical to, or at least very similar to, those found in CF. This assumption has not been tested. The underlying pathophysiology of PCD is not the same as CF and may cause bronchiectasis that is radiologically similar but not necessarily the same as CF or any other cause of bronchiectasis. The development of a disease specific scoring system for structural change in cases of non-CF bronchiectasis due to any cause, would require consideration of the full range of changes seen in that condition without reference to changes seen in other conditions. We present a summary of structural findings that have been described in PCD and highlight the radiological differences between PCD and other causes of bronchiectasis. We suggest that a PCD specific CT scoring system is required to properly describe changes seen in PCD.

Severe but not moderate hyperoxia of newborn mice causes an emphysematous lung phenotype in adulthood without persisting oxidative stress and inflammation

BackgroundPreterm newborns typically require supplemental oxygen but hyperoxic conditions also damage the premature lung. Oxygen-induced lung damages are mainly studied in newborn mouse models using oxygen concentrations above 75% and looking at short-term effects. Therefore, we aimed at the investigation of long-term effects and their dependency on different oxygen concentrations.MethodsNewborn mice were exposed to moderate vs. severe hyperoxic air conditions (50 vs. 75% O2) for 14 days followed by a longer period of normoxic conditions. Lung-related parameters were collected at an age of 60 or 120 days.ResultsSevere hyperoxia caused lower alveolar density, enlargement of parenchymal air spaces and fragmented elastic fibers as well as higher lung compliance with peak airflow limitations and higher sensitivity to ventilation-mediated damages in later life. However, these long-term lung structural and functional changes did not restrict the voluntary physical activity. Also, they were not accompanied by ongoing inflammatory processes, increased formation of reactive oxygen species (ROS) or altered expressions of antioxidant enzymes (superoxide dismutases, catalase) and lung elasticity-relevant proteins (elastin, pro-surfactant proteins) in adulthood. In contrast to severe hyperoxia, moderate hyperoxia was less lung damaging but also not free of long-term effects (higher lung compliance without peak airflow limitations, increased ROS formation).ConclusionsSevere but not moderate neonatal hyperoxia causes emphysematous lungs without persisting oxidative stress and inflammation in adulthood. As the existing fragmentation of the elastic fibers seems to play a pivotal role, it indicates the usefulness of elastin-protecting compounds in the reduction of long-term oxygen-related lung damages.

Incidental Findings of Computed Tomography Angiography in Patients Suspected to Pulmonary Embolism; a Brief Report.

Computed tomography pulmonary angiography (CTPA) scans are increasingly used in emergency department (ED). Therefore, the observation of incidental findings (IFs) has also increased. This study aimed to evaluate the frequency of IFs in patients who underwent CTPA. All consecutive patients that underwent CTPA scanning for pulmonary embolism (PE) rule out between January 2017 and June 2018 were analysed. Incidental findings were divided into and reported in three categories: group 1 potentially life-threatening, group 2 required follow up, and group 3 with limited clinical significance. 151 cases with the mean age of 61.2 ± 17.6 years were studied (54.3% female). PE was documented in 77 cases (50.9%). 448 IFs were detected (3 IFs were found per patient). 60 (13.3%) IFs were classified as group 1, 180 (40.1%) as group 2, and 208 (46.6%) as group 3. Cardiomegaly was the most frequent finding in group 1 (n=32), followed by aortic aneurysm (n=13). In group 2, pleural effusion (n=58) and pneumonia (n=36) were the most frequent incidental findings. Lung structure changes (n=92) and thoracic bone related findings (n=43) were the most common IFs observed in group 3. IFs were detected in the majority of patients that underwent CTPA. Most of these findings do not require follow-up or treatment. However, more than 50% of cases may require further diagnostic evaluation (40.1%) or immediate treatment (13.3%).

Multi-walled carbon nanotubes activate and shift polarization of pulmonary macrophages and dendritic cells in an in vivo model of chronic obstructive lung disease

With substantial progress of nanotechnology, there is rising concern about possible adverse health effects related to inhalation of nanomaterials, such as multi-walled carbon nanotubes (MWCNT). In particular, individuals with chronic respiratory disorders, such as chronic obstructive pulmonary disease (COPD), may potentially be more susceptible to adverse health effects related to inhaled MWCNT. Hazard assessment of such inhaled nanomaterials therefore requires timely clarification. This was assessed in this study using a mouse model of COPD by exposing animals to 0.08 µg/cm2 of MWCNT administered by intratracheal instillation. Treatment with MWCNT induced an accumulation of alveolar macrophages (AMφ) in bronchoalveolar lavage fluid (BALF) in COPD mice that increased from 24 h to 7 d. In COPD mice, MWCNT induced a dynamic shift in macrophage polarization as measured by expression of CD38 and CD206, and increased AMφ and lung parenchyma macrophage (LPMΦ) activation with upregulation of co-stimulatory markers CD40 and CD80. Moreover, MWCNT treatment increased the frequencies of pulmonary dendritic cells (DC), leading to an expansion of the CD11b+CD103− DC subset. Although MWCNT did not trigger lung functional or structural changes, they induced an increased expression of the muc5AC transcript in mice with COPD. Our data provide initial evidence that inhaled MWCNT affect the pulmonary mucosal immune system by altering the numbers, phenotype, and activation status of antigen-presenting cell populations. Extrapolating these in vivo mouse findings to human pulmonary MWCNT exposure, caution is warranted in limiting exposure when handling inhalable nanofibers.

Features of microscopic changes in lung structure of young rats under conditions of hyperhomocysteinemia

Hyperhomocysteinemia is a risk factor for many diseases, including pathologies of the respiratory system. The pathogenesis of lung tissue damage is complex and multifactorial, however, it has now been found that homocysteine has a toxic effect on the vascular system and parenchyma of the organ. The purpose of the study is to identify the features of microscopic changes in the structure of the lungs of young rats under conditions of hyperhomocysteinemia. The experimental study was performed on 22 white non-linear young (1-2 months) male rats. During the experiment, the animals were divided into two groups – control and experimental. Simulation of persistent hyperhomocysteinemia was achieved by administering to rats of the experimental group thiolactone homocysteine at a dose of 200 mg/kg body weight intragastrically for 60 days. Histological specimens were examined using an SEO SCAN light microscope and photo-documented using a Vision CCD Camera with the system output images of histological preparations. It was found that the introduction of thiolactone homocysteine to young rats at a dose of 200 mg/kg led to the development of destructive changes in blood vessels, bronchi, components of the respiratory department with signs of atelectasis. Hemodynamic disorders and increased vascular permeability led to perivascular, peribronchial, interstitial, intra-alveolar edema, histo-leukocyte infiltration. The detected changes are reversible and have a compensatory nature.

Local Administration of Caloric Restriction Mimetics to Promote the Immune Control of Lung Metastases.

Caloric restriction mimetics (CRMs), compounds that mimic the biochemical effects of nutrient deprivation, administered via systemic route promote antitumor effects through the induction of autophagy and the modulation of the immune microenvironment; however, collateral effects due to metabolic changes and the possible weight loss might potentially limit their administration at long term. Here, we investigated in mice local administration of CRMs via aerosol to reduce metastasis implantation in the lung, whose physiologic immunosuppressive status favors tumor growth. Hydroxycitrate, spermidine, and alpha-lipoic acid, CRMs that target different metabolic enzymes, administered by aerosol, strongly reduced implantation of intravenously injected B16 melanoma cells without overt signs of toxicity, such as weight loss and changes in lung structure. Cytofluorimetric analysis of lung immune infiltrates revealed a significant increase of alveolar macrophages and CD103+ dendritic cells in mice treated with CRMs that paralleled an increased recruitment and activation of both CD3 T lymphocytes and NK cells. These effects were associated with the upregulation of genes related to M1 phenotype, as IL-12 and STAT-1, and to the decrease of M2 genes, as IL-10 and STAT-6, in adherent fraction of lung immune infiltrate, as revealed by real-time PCR analysis. Thus, in this proof-of-principle study, we highlight the antitumor effect of CRM aerosol delivery as a new and noninvasive therapeutic approach to locally modulate immunosurveillance at the tumor site in the lung.

Dermal exposure determines the outcome of repeated airway exposure in a long-term chemical-induced asthma-like mouse model

BackgroundExposure to diisocyanates is an important cause of occupational asthma (OA) in the industrialized world. Since OA occurs after long-term exposure to diisocyanates, we developed a chronic mouse model of chemical-induced asthma where toluene diisocyanate (TDI) was administered at two different exposure sites. ObjectivesEvaluating the effect of long-term respiratory isocyanate exposure - with or without prior dermal exposure- on sensitization, inflammatory responses and airway hyperreactivity (AHR). MethodsOn days 1 and 8, BALB/c mice were dermally treated (20 μl/ear) with 0.5% 2,4-toluene diisocyanate TDI or the vehicle acetone olive oil (AOO) (3:2). Starting from day 15, mice received intranasal instillations with 0.1% TDI of vehicle five times in a week, for five successive weeks. One day after the last instillation airway hyperreactivity (AHR) to methacholine was assessed, followed by an evaluation of pulmonary inflammation and structural lung changes. Immune-related parameters were assessed in the lungs (BAL and tissue), blood, cervical- and auricular lymph nodes. ResultsMice repeatedly intranasally exposed to TDI showed systemic sensitization and a mixed Th1/Th2 type immune response, without the presence of AHR. However, when mice are first dermally sensitized with TDI, followed by repeated intranasal TDI challenges, this results in a pronounced Th2 response and AHR. ConclusionDermal exposure to TDI determines airway hyperreactivity after repeated airway exposure to TDI.

Altered relaxation times in MRI indicate bronchopulmonary dysplasia

We developed a MRI protocol using transverse (T2) and longitudinal (T1) mapping sequences to characterise lung structural changes in preterm infants with bronchopulmonary dysplasia (BPD). We prospectively enrolled 61 infants...

Association of respiratory integer and fractional-order models with structural abnormalities in silicosis

Background and objectiveInteger and fractional-order models have emerged as powerful methods for obtaining information regarding the anatomical or pathophysiological changes that occur during respiratory diseases. However, the precise interpretation of the model parameters in light of the lung structural changes is not known. This study analyzed the associations of the integer and fractional-order models with structural changes obtained using multidetector computed tomography densitometry (MDCT) and pulmonary function analysis. MethodsInteger and fractional-order models were adjusted to data obtained using the forced oscillation technique (FOT). The results obtained in controls (n = 20) were compared with those obtained in patients with silicosis (n = 32), who were submitted to spirometry, body plethysmograph, FOT, diffusing capacity of the lungs for carbon monoxide (DLCO), and MDCT. The diagnostic accuracy was also investigated using ROC analysis. ResultsThe observed changes in the integer and fractional-order models were consistent with the pathophysiology of silicosis. The integer-order model showed association only between inertance and the non-aerated compartment (R = −0.69). This parameter also presented the highest associations with spirometry (R = 0.81), plethysmography (−0.61) and pulmonary diffusion (R = 0.53). Considering the fractional-order model, the increase in the poorly aerated and non-aerated regions presented direct correlations with the fractional inertance (R = 0.48), respiratory damping (R = 0.37) and hysteresivity (R = 0.54) and inverse associations with its fractional exponent (R = −0.62) and elastance (−0.35). Significant associations were also observed with spirometry (R = 0.63), plethysmography (0.37) and pulmonary diffusion (R = 0.51). Receiver operator characteristic analysis showed a higher accuracy in the FrOr model (0.908) than the eRIC model (0.789). ConclusionsOur study has shown clear associations of the integer and fractional-order parameters with anatomical changes obtained via MDCT and pulmonary function measurements. These findings help to elucidate the physiological interpretation of the integer and fractional-order parameters and provide evidence that these parameters are reflective of the abnormal changes in silicosis. We also observed that the fractional-order model showed smaller curve-fitting errors, which resulted in a higher diagnostic accuracy than that of the eRIC model. Taken together, these results provide strong motivation for further studies exploring the clinical and scientific use of these models in respiratory medicine.

Profound Increase of Lung Airway Resistance in Heart Failure: a Potential Important Contributor for Dyspnea.

Dyspnea is a major symptom of heart failure (HF). Here, we have studied the lung remodeling and airway resistance in HF mice. We demonstrated that aortic banding-induced HF caused a dramatic decrease of lung compliance and an increase of lung airway resistance. The decrease of lung compliance was correlated with the increased lung weight in a linear fashion (γ2 = 0.824). An HF-induced increase of lung airway resistance and a decrease of lung compliance were almost identical in anesthetized mice and in the isolated lungs from these mice. HF caused profound lung fibrosis in mice with increased lung weight. Moreover, HF patients of NYHA class III-IV showed increased lung density as revealed by high-resolution CT scanning. These data indicate that lung compliance and lung airway resistance may be useful in determining lung remodeling after HF, and lung structure changes may contribute to dyspnea in HF.