Lung Pathology In Patients Research Articles

Radiological microcirculatory findings in a relatively normal radiological picture of the lungs

Introduction. In clinical practice the state of the lungs could be assessed by a large number of functional, laboratory and instrumental tests, including a powerful approach like radiodiagnosis. Reliable, timely detection of hemodynamic disorders in the lungs, as well as their correct interpretation, are important for effective treatment. Objective. To show the diagnostic significance of SPECT in the detection of lung pathology in patients with a relatively normal radiographic picture. Materials and methods. SPECT data of patients had a relatively normal X-ray picture of the lungs were analyzed to assess changes in lung circulation. Patients (n=176) were divided into groups according to diseases: group 1 – patients (n=78) with post-COVID syndrome; group 2 – patients (n=23) with heart failure, PH; group 3 – patients with vasculitis (n=48); group 4 – patients with lymphoproliferative diseases (n=27) (acute lymphoblastic leukemia, peripheral T-cell lymphoma, diffuse B-cell lymphoma). Results. SPECT was shown to be useful in detecting disorders in the microvasculature of the lungs in patients with various pathologies. The results of X-ray and radionuclide methods were compared for patients with lesions of the bronchopulmonary system. The diagnosis errors of a radiologist caused by non-obvious changes on radiographs of the chest cavity organs were analyzed. Conclusions. Lung radiological examination is a complementary to X-ray method and in some cases it is preferred to establish the causes of the disease due to the higher sensitivity. The radiological algorithm, qualitative and quantitative assessment of the results of radiological examination, allows to detect minimal changes in the lungs.

Feasibility and Safety of Transbronchial Lung Cryobiopsy for Diagnosis of Acute Respiratory Failure with Mechanical Ventilation in Intensive Care Unit.

Acute hypoxemic respiratory failure is common in intensive care units (ICUs). Lung biopsies may be required to make a definitive diagnosis in patients with unknown etiologies. The feasibility of transbronchial lung cryobiopsy is undetermined in patients with respiratory failure in the ICU. Patients who underwent bronchoscopy examinations with transbronchial lung cryobiopsy (TBLC) between July 2018 and December 2019 were retrospectively analyzed through medical chart review. The procedures were performed by well-experienced interventional pulmonologists. Ten patients underwent bronchoscopy examinations with TBLC in the ICU at Chang Gung Memorial Hospital during the study period. In all patients, the diagnosis was made via pathological analysis. One patient developed pneumothorax and required chest tube placement after the procedure. None of the patients had bleeding requiring blood transfusion, and no deaths were directly related to the procedure. TBLC is a feasible technique to obtain lung pathology in patients with acute respiratory diseases of unknown etiologies. While the complication rate may be acceptable, the procedure should be performed by experienced interventional pulmonologists. However, airway blockers and fluoroscopy are highly recommended when used according to the current guideline. We do not encourage TBLC to be performed without having airway blockers available at the bedside.

Relevance of Bedside lung Ultrasound in Emergency protocol (BLUE protocol) in the diagnosis of lung pathology in patients with respiratory failure admitted to intensive Care Unit

Relevance of Bedside lung Ultrasound in Emergency protocol (BLUE protocol) in the diagnosis of lung pathology in patients with respiratory failure admitted to intensive Care Unit

D-dimer and CoV-2 spike-immune complexes contribute to the production of PGE2 and proinflammatory cytokines in monocytes.

An overreactive inflammatory response and coagulopathy are observed in patients with severe form of COVID-19. Since increased levels of D-dimer (DD) are associated with coagulopathy in COVID-19, we explored whether DD contributes to the aberrant cytokine responses. Here we show that treatment of healthy human monocytes with DD induced a dose dependent increase in production of pyrogenic mediator, Prostaglandin E2 (PGE2) and inflammatory cytokines, IL-6 and IL-8. The DD-induced PGE2 and inflammatory cytokines were enhanced significantly by co-treatment with immune complexes (IC) of SARS CoV-2 recombinant S protein or of pseudovirus containing SARS CoV-2 S protein (PVCoV-2) coated with spike-specific chimeric monoclonal antibody (MAb) containing mouse variable and human Fc regions. The production of PGE2 and cytokines in monocytes activated with DD and ICs was sensitive to the inhibitors of β2 integrin and FcγRIIa, and to the inhibitors of calcium signaling, Mitogen-Activated Protein Kinase (MAPK) pathway, and tyrosine-protein kinase. Importantly, strong increase in PGE2 and in IL-6/IL-8/IL-1β cytokines was observed in monocytes activated with DD in the presence of IC of PVCoV-2 coated with plasma from hospitalized COVID-19 patients but not from healthy donors. The IC of PVCoV-2 with convalescent plasma induced much lower levels of PGE2 and cytokines compared with plasma from hospitalized COVID-19 patients. PGE2 and IL-6/IL-8 cytokines produced in monocytes activated with plasma-containing IC, correlated well with the levels of spike binding antibodies and not with neutralizing antibody titers. Our study suggests that a combination of high levels of DD and high titers of spike-binding antibodies that can form IC with SARS CoV-2 viral particles might accelerate the inflammatory status of lung infiltrating monocytes leading to increased lung pathology in patients with severe form of COVID-19.

Evaluation of COVID-19-Associated Myocarditis Via Point-of-Care Ultrasound in a Pediatric Patient.

Coronavirus disease 2019 (COVID-19)-associated myocarditis has been reported from the onset of the pandemic. The presumed etiology is direct damage to the myocardium from severe acute respiratory syndrome coronavirus 2. Common findings include electrocardiogram abnormalities, elevated cardiac markers, and diminished cardiac function. This can lead to heart failure and cardiogenic shock with resultant poor perfusion. Thus, myocarditis has been recognized as a cause of death in patients with COVID-19. Unfortunately, it is difficult to predict the prevalence of myocarditis in these patients given the relative novelty of the pandemic and the lack of available data. Point-of-care ultrasound (POCUS) has been shown to be a useful modality to investigate lung pathology in patients with COVID-19. Bedside cardiac POCUS can also be used to investigate cardiac pathology. This case describes a pediatric patient with COVID-19 who had evidence of myocarditis on POCUS in the pediatric emergency department.

Lung Pathology in Patients with Acute Respiratory Distress Syndrome Associated with the Novel SARS-Cov-2 Virus

Acute Respiratory Distress Syndrome (ARDS) is a well-recognized clinical problem first described in the late sixties. However, its relevance seems to have increased since the severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) outbreak, as 14% (CI 95% 2% to 59%) of patients admitted to the hospital present with this syndrome. Conceptually, a syndrome is a group of symptoms and signs that correspond to several diseases. Although defining disease is much harder than may appear at first glance, we can view it as the association between a syndrome and a pathology pattern. Diffuse alveolar damage (DAD) is the morphological hallmark of ARDS, although studies performed in autopsies and patients have demonstrated that it is present in only half of ARDS patients. The SARS-CoV-2 outbreak and the high incidence of ARDS associated with this infection have triggered a natural question: is the lung pathology similar in patients with ARDS associated with traditional risk factors than to SARS-CoV-2 infection? This review aims to analyze the lung pathology results of patients infected with the novel SARS Cov-2. As this article targets non-intensive care physicians, we will first describe the main characteristics of the novel SARS-Cov-2 and the ARDS definition, and then the lung pathology results from the UCI in this group of patients.

A Defect in Thymic Tolerance Causes T Cell-Mediated Autoimmunity in a Murine Model of COPA Syndrome.

COPA syndrome is a recently described Mendelian autoimmune disorder caused by missense mutations in the coatomer protein complex subunit α (COPA) gene. Patients with COPA syndrome develop arthritis and lung disease that presents as pulmonary hemorrhage or interstitial lung disease (ILD). Immunosuppressive medications can stabilize the disease, but many patients develop progressive pulmonary fibrosis, which requires life-saving measures, such as lung transplantation. Because very little is understood about the pathogenesis of COPA syndrome, it has been difficult to devise effective treatments for patients. To date, it remains unknown which cell types are critical for mediating the disease as well as the mechanisms that lead to autoimmunity. To explore these issues, we generated a CopaE241K/+ germline knock-in mouse bearing one of the same Copa missense mutations in patients. Mutant mice spontaneously developed ILD that mirrors lung pathology in patients, as well as elevations of activated cytokine-secreting T cells. In this study, we show that mutant Copa in epithelial cells of the thymus impairs the thymic selection of T cells and results in both an increase in autoreactive T cells and decrease in regulatory T cells in peripheral tissues. We demonstrate that T cells from CopaE241K/+ mice are pathogenic and cause ILD through adoptive transfer experiments. In conclusion, to our knowledge, we establish a new mouse model of COPA syndrome to identify a previously unknown function for Copa in thymocyte selection and demonstrate that a defect in central tolerance is a putative mechanism by which COPA mutations lead to autoimmunity in patients.

Point-of-care lung ultrasound for diagnosis of Pneumocystis jirovecii pneumonia: notes from the field

BackgroundThoracic ultrasound is helpful to evaluate lung pathology in patients with acute dyspnea. Several studies have demonstrated the efficacy of point-of-care ultrasound in patients with extrapulmonary TB and HIV co-infection. This retrospective, open-label case–control study explores the role of lung ultrasound in the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in HIV-positive patients. In particular, it highlights the potential role of specific sonographic features that may be unique to this population.MethodsThe record of all HIV-positive patients admitted from 1.1.2013 to 31.6.2017 to the Department of Infectious Diseases and Tropical Medicine of san Bortolo Hospital, Vicenza, Italy, with a discharge diagnosis of acute lung injury (ALI) and who received point-of-care ultrasound of the chest for clinical purposes was included in the analysis. The patients were scanned according with the evidence-based recommendation.ResultsOf 273 HIV-positive patients whose records were reviewed, 81 (29.6%) were diagnosed with ALI. Complete documentation was available for 24 patients, of which 14 (58.3%) had microbiologically confirmed PJP (PJP+) and 10 (41.7%) had other conditions (PJP−). B-lines, subpleural consolidations, and cystic changes were significantly more frequent in patients with PJP (14/14 vs. 6/10, p = 0.0198; 14/14 vs. 4/10, p = 0.0016; 8/14 vs. 0/10, p = 0.0019, respectively). In particular, B-lines and subpleural consolidations were present in all PJP+ patients in our cohort giving a sensitivity of 100%, but their specificity was low (45 and 60%, respectively). On the contrary, the presence of consolidations with cystic changes had a very high specificity for PJP (100%), but low sensitivity (57%). Pleural effusions and consolidations with linear air bronchograms were not observed in PJP+ patients.ConclusionsB-lines, subpleural consolidations, and cystic changes are suggestive of PJP. Lung consolidation with air bronchograms and pleural effusion should prompt suspicion of other etiologies. These findings have the potential to be useful in the daily management of HIV-positive patients in resource-limited settings where other diagnostic tools are rarely available.

Increased susceptibility of Cftr-/- mice to LPS-induced lung remodeling.

Cystic fibrosis (CF) is caused by homozygous mutations of the CF transmembrane conductance regulator (CFTR) Cl(-) channel, which result in chronic pulmonary infection and inflammation, the major cause of morbidity and mortality. Although these processes are clearly related to each other, each is likely to contribute to the pathology differently. Understanding the contribution of each of these processes to the overall pathology has been difficult, because they are usually so intimately connected. Various CF mouse models have demonstrated abnormal immune responses compared with wild-type (WT) littermates when challenged with live bacteria or bacterial products acutely. However, these studies have not investigated the consequences of persistent inflammation on lung tissue in CF mice, which may better model the lung pathology in patients. We characterized the lung pathology and immune response of Cftr(-/-) (CF) and Cftr(+/+) (WT) mice to chronic administration of Pseudomonas aeruginosa lipopolysaccharide (LPS). We show that, after long-term repeated LPS exposure, CF mice develop an abnormal and persistent immune response, which is associated with more robust structural changes in the lung than those observed in WT mice. Although CF mice and their WT littermates develop lung pathology after chronic exposure to LPS, the inflammation and damage resolve in WT mice. However, CF mice do not recover efficiently, and, as a consequence of their chronic inflammation, CF mice are more susceptible to morphological changes and lung remodeling. This study shows that chronic inflammation alone contributes significantly to aspects of CF lung pathology.

A MicroRNA Processing Defect in Smokers' Macrophages Is Linked to SUMOylation of the Endonuclease DICER

Despite the fact that alveolar macrophages play an important role in smoking-related disease, little is known about what regulates their pathophysiologic phenotype. Evaluating smoker macrophages, we found significant down-regulation of multiple microRNAs (miRNAs). This work investigates the hypothesis that cigarette smoke alters mature miRNA expression in lung macrophages by inhibiting processing of primary miRNA transcripts. Studies on smoker alveolar macrophages showed a defect in miRNA maturation. Studies on the miRNA biogenesis machinery led us to focus on the cytosolic RNA endonuclease, DICER. DICER cleaves the stem-loop structure from pre-miRNAs, allowing them to dissociate into their mature 20-22-nucleotide single-stranded form. DICER activity assays confirmed impaired DICER activity following cigarette smoke exposure. Further protein studies demonstrated a decreased expression of the native 217-kDa form of DICER and an accumulation of high molecular weight forms with cigarette smoke exposure. This molecular mass shift was shown to contain SUMO moieties and could be blocked by silencing RNA directed at the primary SUMOylating ligase, Ubc9. In determining the cigarette smoke components responsible for changes in DICER, we found that N-acetylcysteine, an antioxidant and anti-aldehyde, protected DICER protein and activity from cigarette smoke extract. This massive down-regulation of miRNAs (driven in part by alterations in DICER) may be an important regulator of the disease-promoting macrophage phenotype found in the lungs of smokers.

Novel in vitro respiratory models to study lung development, physiology, pathology and toxicology

Detailed studies of lung pathology in patients during the course of development of acute lung injury or respiratory distress are limited, and in the past information related to lung-specific responses has been derived from the study of lungs from patients who died at autopsy or from animal models. Development of good in vitro human tissue models would help to bridge the gap in our current knowledge of lung responses and provide a better understanding of lung development, physiology and pathology. In vitro models of simple one-cell or two-cell culture systems as well as complex multicellular lung analogs that reproduce defined components of specific human lung responses have already been realized. A benefit of current in vitro lung models is that hypotheses generated from review of data from human or animal disease studies can be tested directly in engineered human tissue models. Results of studies done using simple in vitro lung systems or more complex three-dimensional models have already been used to examine cell-based responses, physiologic functions, pathologic changes and even drug toxicity or drug responses. In the future we will create models with specific genetic profiles to test the importance of single gene products or pathways of significance. Recent development of microfluidics-based models that support high-throughput screening will allow early-stage toxicity testing in human systems and faster development of new and innovative medical products. Model design in the future will also allow for evaluation of multiple organ systems at once, providing a more holistic or whole-body approach to understanding human physiology and responses.

High-resolution computed tomography in detection of lung pathology in patients with connective tissue dysplasia

Summary. This article presents results of examination of 50 young patients with connective tissue dysplasia not having any acute or chronic respiratory disease. All patients underwent inspiratory and expiratory helical CT with density gradient determination in different parts of the lungs. Typical CT findings were subpleural apical bullae and bleby (16 %), peribronchial fibrosis (40 %), local fibrosis (18 %), plevroapikal spikes (62 %), emphysema (4 %), air traps (18 %). The density gradient between exhalation and inhalation was reduced in the upper and lower lobes of the lungs.

Updating Our Understanding of Pulmonary Disease Associated With HIV Infection

The introduction of highly active antiretroviral therapy (HAART) has resulted in a reduction of opportunistic infections associated with cellular and humoral immunosuppression. However, what is still unclear is the impact of HAART on the development of other diseases not associated with AIDS, such as lung cancer and COPD. The aim of this paper is to review the most innovative and relevant aspects of lung pathology in patients infected with HIV.

Actualización en la patología pulmonar relacionada con la infección VIH

The introduction of highly active antiretroviral therapy (HAART) has resulted in a reduction of opportunistic infections associated with cellular and humoral immunosuppression. However, what is still unclear is the impact of HAART on the development of other diseases not associated with AIDS, such as lung cancer and COPD. The aim of this paper is to review the most innovative and relevant aspects of lung pathology in patients infected with HIV.

Angiotensin receptor blockade attenuates cigarette smoke–induced lung injury and rescues lung architecture in mice

Chronic obstructive pulmonary disease (COPD) is a prevalent smoking-related disease for which no disease-altering therapies currently exist. As dysregulated TGF-β signaling associates with lung pathology in patients with COPD and in animal models of lung injury induced by chronic exposure to cigarette smoke (CS), we postulated that inhibiting TGF-β signaling would protect against CS-induced lung injury. We first confirmed that TGF-β signaling was induced in the lungs of mice chronically exposed to CS as well as in COPD patient samples. Importantly, key pathological features of smoking-associated lung disease in patients, e.g., alveolar injury with overt emphysema and airway epithelial hyperplasia with fibrosis, accompanied CS-induced alveolar cell apoptosis caused by enhanced TGF-β signaling in CS-exposed mice. Systemic administration of a TGF-β-specific neutralizing antibody normalized TGF-β signaling and alveolar cell death, conferring improved lung architecture and lung mechanics in CS-exposed mice. Use of losartan, an angiotensin receptor type 1 blocker used widely in the clinic and known to antagonize TGF-β signaling, also improved oxidative stress, inflammation, metalloprotease activation and elastin remodeling. These data support our hypothesis that inhibition of TGF-β signaling through angiotensin receptor blockade can attenuate CS-induced lung injury in an established murine model. More importantly, our findings provide a preclinical platform for the development of other TGF-β-targeted therapies for patients with COPD.

Pulmonary Complications After Acute Kidney Injury

The development of respiratory failure in patients with AKI is a particularly devastating consequence that greatly increases patient mortality. When respiratory failure and AKI occur together, the mortality is greater than 80%. A clear understanding of the mechanisms leading to respiratory failure is of great clinical relevance to patients with AKI in order to prevent and treat this life-threatening complication. Pulmonary edema leading to respiratory failure has been a recognized complication of kidney failure since 1901. Remarkably, the pathogenesis of this complication remains elusive, despite over 100 years of clinical and experimental debate in the literature. A review of this literature suggests that there are 4 causes of pulmonary edema leading to respiratory failure in patients with AKI: (1) volume overload (cardiogenic edema), (2) left ventricular dysfunction (cardiogenic edema), (3) increased lung capillary permeability (noncardiogenic edema), and (4) acute lung injury (noncardiogenic edema with inflammation). In this review, these mechanisms are presented in historical context including the original descriptions of pathology and pathophysiology, recent epidemiologic data, and experimental studies in animals. Although volume overload is a well-accepted mechanism of pulmonary edema in patients with AKI, the purpose of this review was to highlight the evidence showing that noncardiogenic edema and acute lung injury also occur. By recognizing that the pulmonary complications of AKI are not simply from volume overload, specific treatment strategies may be discovered and used to improve outcomes in patients with the ominous and life threatening combination of AKI and respiratory failure.

Mustard lung secrets: Long term clinicopathological study following mustard gas exposure

Considering the undefinite nature of lung pathology in patients exposed to sulfur mustard (SM) many years after exposure, we conducted this study to document and quantify lung disease in this setting. In a cross sectional study, we selected 23 patients exposed to SM gas approximately 14 years ago during the Iran–Iraq war (1980–1988). We studied their clinical history, physical examination, pulmonary function test (PFT), high-resolution computed tomography scan (HRCT) of the chest, bronchoscopy, and bronchoalveolar lavage (BAL) sampling, and transbronchial lung biopsies. Other potential causes of lung disease, including smoking of cigarettes, were excluded. All 23 patients were symptomatic with cough, dyspnea, and/or felt tight in the chest. All of them had significant air trapping in HRCT and a marked increase of residual volume in PFT. The most common inflammatory cell in BAL fluid was neutrophil (88%). Of the 23 cases, there was sufficient tissue for detailed evaluation in 22. Histologically, 11 cases showed airway epithelial injury, and nine of the 14 lung biopsies with alveoli had histopathological changes diagnosable as organizing pneumonia (OP) or bronchiolitis obliterans OP (BOOP). Two out of 14 cases showed changes suggestive of OP. Inhalation of SM can lead to persistant and clinically significant lung disease, including bronchial mucosal injury and OP, many years after exposure.

Lung pathology in patients with congenital diaphragmatic hernia treated with fetal surgical intervention, including tracheal occlusion.

Fetal intervention for congenital diaphragmatic hernia was developed to lessen the high morbidity and mortality of pulmonary hypoplasia. Lung pathology and morphometry in patients treated with fetal intervention have not been described. We report clinical and autopsy findings, as well as basic lung morphometry in 16 cases of congenital diaphragmatic hernia with fetal intervention (12 cases tracheal occlusion; 4 cases hernia repair), and 19 cases of congenital diaphragmatic hernia without fetal intervention. All patients who underwent fetal intervention were born premature. Lung enlargement with increased lung-to-body weight ratio was observed with fetal tracheal occlusion, accompanied by lower than normal radial alveolar counts and increased alveolar size. Patients treated with tracheal occlusion also had early alveolar development (at 29.8, 30.6, and 30.9 wk postconceptual age) as well as mucous fluid pooling in airways and alveoli. All cases showed severe alveolar septal widening, more extensive in patients without fetal intervention. When grouped by postconceptual age, no statistically significant difference was found between patients with and without fetal intervention with respect to lung-to-body weight ratio, radial alveolar count, mean alveolar length, and relative arteriolar media thickness. Lung enlargement has been observed with fetal tracheal occlusion sonographically; our studies suggest that this is due in part to emphysema and mucous fluid pooling. The lung remains abnormal with low radial alveolar counts and increased alveolar size. Tracheal occlusion did not prevent development of lung pathology associated with pulmonary hypoplasia.

Noninfectious lung pathology in patients with Crohn's disease.

Lung involvement in Crohn's disease is not well characterized. We reviewed our experience with 11 lung biopsies (seven wedge and four transbronchial) from patients with Crohn's disease to study this association further. Negative cultures, special stains for organisms Gomori-methenamine-silver [GMS], acid fast), and polymerase chain reaction for (four cases) were required for inclusion. The group included five women and six men with a mean age of 47 years (range 13-84 years). A diagnosis of Crohn's disease preceded the lung disease in nine patients. In two patients the diagnosis of Crohn's disease followed the diagnosis of their pulmonary disease 1 and 15 months later. Radiologically, eight patients had diffuse infiltrates, two had bilateral nodular infiltrates, and one had a mass. Chronic bronchiolitis with nonnecrotizing granulomatous inflammation was present in four patients, one of whom was taking mesalamine. Two patients had an acute bronchiolitis associated with a neutrophil-rich bronchopneumonia with suppuration and vague granulomatous features. One patient on mesalamine had cellular interstitial pneumonia with rare giant cells. Four patients demonstrated organizing pneumonia with focal granulomatous features, two of whom were taking mesalamine, and one of these two responded to infliximab (anti-tumor necrosis factor) monoclonal antibody therapy. Noninfectious pulmonary disease in patients with Crohn's disease has variable histologic appearances, including granulomatous inflammation and airway-centered disease resembling that seen in patients with ulcerative colitis. Drugs may contribute to pulmonary disease in some patients.