Pulmonary Alveolar Research Articles

Pulmonary Alveolar Proteinosis in a Three-month-old Infant: An Unusual Case Report

Pulmonary Alveolar Proteinosis (PAP) is an unusual diffuse lung disease characterised by the alveolar accumulation of phospholipoprotein material, with a peak incidence in the 3rd to 4th decades of life and a male predominance. However, it has also been described in children. The recorded prevalence is 0.1 per 100,000 individuals. The major clinicopathogenetic subtypes include the autoimmune (idiopathic) form, which is associated with Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) autoantibodies, the secondary form and the congenital form (associated with surfactant gene mutations). Common presenting features include dyspnoea, cough, low-grade fever, inspiratory crackles and digital clubbing. Pulmonary function tests typically show restrictive ventilatory defects. Herein, the authors present a case of a three-month-old male infant who presented with cough, dyspnoea and failure to thrive over the past 10 days. X-rays revealed a bilateral reticular pattern with non homogeneous opacities. Computed Tomography (CT) of the chest showed features consistent with interstitial lung disease. High-resolution Computed Tomography (HRCT) demonstrated a crazy-paving appearance, suggestive of interstitial lung disease or a surfactant-related genetic disorder. Bronchial Alveolar Lavage (BAL) yielded milky fluid. Characteristic microscopic findings on lung biopsy included the filling of terminal bronchioles and alveolar spaces with deep pink granular Periodic Acid Schiff (PAS)-positive eosinophilic material, while the alveolar architecture remained preserved. Patients with minimal symptoms are managed conservatively, whereas those with hypoxaemia require a more aggressive approach. Whole Lung Lavage (WLL) is the safest and most effective form of treatment. To date, there have been 240 case reports and 410 case series documented in the literature. This is the first case of PAP reported in the study institution. The authors present this case report here due to its rarity and diagnostic significance.

ЛЕГЕНЕВИЙ АЛЬВЕОЛЯРНИЙ ПРОТЕЇНОЗ: ВИПАДОК СУБТОТАЛЬНОГО УРАЖЕННЯ ПАРЕНХІМИ ЛЕГЕНЬ)

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease, characterized by the intraalveolar accumulation of surfactant-like lipoprotein substance. There are three forms of the disease: autoimmune (formerly known as idiopathic), secondary and congenital PAP. The disturbances of surfactant metabolism (protein-lipoid complex secreted by type II pneumocytes) play the crucial role in the development of the disease. Surfactant decreases a surface tension of alveoli and prevents its collapse at the end of the expiration and takes part in protection against infections as well. Surfactant is inactivated through the transformation into the surface-inactive aggregates, which are mainly absorbed by type II pneumocytes. The rest of surfactant are catabolized by alveolar macrophages (AM). This process is regulated by cytokines, especially granulocyte-macrophage colony-stimulating factor (GM-CSF) being the most important of them. Disturbances of interrelation between GM-CSF and cellular receptors blocks the signals to effector cells for surfactant deactivation. This is resulted in excessive accumulation of surfactant in alveoli. General lavage of the lung is a standard method of symptomatic management of PAP. Contemporary pathogenesis treatment uses two approaches — increasing the clearance of surfactant by means of exogenous GM-CSF administration and decreasing the level of GM-CSF antibodies using the rituximab and plasmapheresis. Due to the use of broncho-alveolar lavage (BAL) 5-year survival rate of th patients reaches 95 %. The mortality depends on the area of lung lesion and reversely correlated with the timely diagnosis and treatment. We report the case of subtotal lung parenchyma lesion associated with severe respiratory failure in 46 years old patient. Three series of BAL (5 procedures in each with 1-2 months interval) were performed using the limited volume of lavage fluid due to the severity of the patient’s condition. The results was an improvement of clinical condition, resolution of respiratory failure, significant reduction of the size of the lesions, improved lung transparency on CT scan, restoration of lung diffusion and total lung capacity. Conclusion. Therapeutic BAL is an effective method of PAP management. The outcome of clinical case presented and our many years experience confirm not only the effectiveness of conventional BAL with reduced lavage volume application but also a safety of fiberoptic bronchoscopy, especially in patients with subtotal involvement of lung parenchyma. Key words: pulmonary alveolar proteinosis, subtotal pulmonary parenchyma involvement, pulmonary bronchoalveolar lavage, efficiency.

IL-17 Mildly Rescued the Impaired Proliferation of Alveolar Epithelial Cells Induced by LCN2 Overexpression.

The impaired proliferative capacity of alveolar epithelial cells after injury is an important factor causing epithelial repair dysfunction, leading to the occurrence of idiopathic pulmonary fibrosis (IPF). Alveolar type 2 (AT2) cells as the stem cells of alveolar epithelium participate in the repair process after alveolar injury. Lipocalin-2 (LCN2) participates in multiple processes regulating the pathological process of alveolar epithelial cells, but the mechanisms involved are still unclear. We used a BLM-treated mouse model to characterize the expression of LCN2 in lung fibrosis regions and analyzed the location of LCN2 in alveolar epithelial cells. Moreover, human pulmonary alveolar epithelial cells (HPAEpiCs) were transfected with the LCN2 overexpression plasmid vector in vitro. Recombinant human interleukin-17 (IL-17) protein (rhIL-17) at different concentrations was administered to intervene in HPAEpiCs, observing cell viability and analyzing the concentration-dependent effect of IL-17. LCN2 was increased in the alveolar epithelium post-BLM injury, and highly expressed LCN2 was mainly concentrated on AT2 cells in BLM-injured lungs. Meanwhile, LCN2-overexpressing HPAEpiCs showed impaired cell viability and cell growth. HPAEpiC intervention with rhIL-17 mildly rescued the impaired cell proliferation induced by LCN2 overexpression, and the effect of IL-17 intervention was partially concentration-dependent. The results revealed the reversed effect of IL-17 on the impaired proliferative capacity of the alveolar epithelium induced by LCN2 overexpression. The target alveolar epithelial cells regulated by this process were AT2 cells, providing new clues for alveolar epithelium repair after injury and the treatment of lung injury diseases.

Diagnostic Value of Serum KL-6 in Interstitial Lung Diseases.

To explore serum KL-6 level and investigate its diagnostic value in interstitial lung diseases (ILDs). Serum KL-6 level was measured using the chemiluminescent enzyme immunoassay. Statistical analysis was performed for determining the KL-6 concentration of each group. KL-6 level (U/mL) in the ILD group was 1388.321 ±1943.116, which was higher than that in the control group, showing a significant statistical difference. ROC curve analysis based on the receiver operating characteristic curve showed the optimal cut-off value of 402.5U/mL, sensitivity of 77.4%, specificity of 93.4%, and accuracy of 89.4%; through Chi-square test with the two groups, the positive rate of KL-6 in patients with ILD was proved to be significantly higher than that in the control group. KL-6 level was 1063.00±504.757 in the idiopathic pulmonary fibrosis (IPF) group, 1346.892 ±1827.252 in the connective tissue disease-associated interstitial lung disease (CTD-ILD) group, 467.889±288.859 in the organizing pneumonia (OP) group, 8252.333±6050.625 in the pulmonary alveolar proteinosis (PAP) group, and 359.200±392.707 in the sarcoidosis group. The rank sum test showed that the differences were statistically significant. KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group. Serum KL-6 level was confirmed to be highly sensitive, specific, and accurate in the diagnosis of ILD. Subgroup analysis showed that the KL-6 level was the lowest in the sarcoidosis group, followed by that in the OP group.

Hereditary Pulmonary Alveolar Proteinosis in a Pediatric Patient – A Diagnostic and Therapeutic Challenge

Abstract The abstract will be: “Pulmonary Alveolar Proteinosis (PAP) is a rare but potentially fatal respiratory disorder. The hereditary form is due to mutations affecting the GM-CSF receptor subunits. We are presenting this case report of a 3-year-old girl -who was the child of a fourth-degree consanguineous marriage- who developed Hereditary Alveolar Proteinosis. Her diagnosis was confirmed by surgical biopsy as well as whole exome sequencing (WES) genetic testing that revealed homozygous gene deletion of the CSF2RA gene (Colony Stimulating Factor 2RA). She had a favorable outcome and spontaneous resolution of her disease on follow-up.”

A Case Report of Pulmonary Alveolar Proteinosis with Associated Opportunistic Infection of Pneumocystis jirovecii and Molluscum Contagiosum

Abstract Pulmonary alveolar proteinosis (PAP) is an idiopathic rare diffuse pulmonary disease, first described in 1958 by Rosen et al. Its estimated prevalence is about 1 in 3.7–6.9 × 106 with a male: female ratio of 1:1–2:1. Majority of the patient’s age ranges between 20 and 50 years. PAP on microscopy is characterized by the presence of massive insoluble, amorphous, phospholipid-rich protein deposits in the bronchial and alveolar cavities. Most patients with acquired PAP present with cough and exertional dyspnea. It has been studied that there is increased risk of superinfection in PAP with opportunistic organisms like pneumocystis and vice versa. Definitive diagnosis of Pneumocystis jirovecii pneumonia rests on the demonstration of the organism within the alveoli by special stains like Grocott Methenamine Silver stain. Molluscum contagiosum (MC) is a common superficial skin infection caused by the poxvirus. MC is characterized by painless papules commonly seen in children and immunocompromised individuals. Here, we present a 34-year-old female who had complaints of severe difficulty in breathing and was brought dead to our hospital. On external examination, she had multiple warts over chest, abdomen, and over genitalia. Internal examination was unremarkable. Specimens of kidney, lung, and skin biopsy of genital warts sent for histopathological examination revealed acute tubular necrosis, P. jirovecii with PAP, and MC respectively.

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According to scientific sources, in 30 % of patients with postCOVID-19 syndrome, additional examination reveals respiratory symptoms, namely a significant decrease in the diffusion capacity of the lungs (DLCO) and associated damage to the pulmonary interstitium. A comparison of interstital lung disease caused by SARS-CoV-2 virus and idiopathic pulmonary fibrosis pathogenesis revealed several common mechanisms: excessive activation of the immune system, secretion of proinflammatory and profibrotic cytokines, damage to the epithelium and endothelium, excessive production of extracellular matrix components, and a decrease in the functional properties of the lungs. Interstitial lung diseases (ILD) is a heterogeneous group characterized by various clinical, radiological, and pathological features that largely affect the lung parenchyma. Pulmonary fibrosis is a characteristic feature of various types of ILD, which are characterized by the presence of chronic inflammation and/or collagen deposition in the interalveolar space, which leads to insufficient passage of oxygen and carbon dioxide molecules through the alveolar epithelium. The presented clinical cases demonstrate the diversity of the pulmonary interstitium lesions in long-COVID, which can be systematized by the correspondingly classified interstitial lung disease. Treatment of these diseases according to the accepted recommendations had a positive effect. Key words: post-COVID-19 syndrome, long-COVID-19, pulmonary fibrosis, interstitial lung diseases, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis.

Our experience in treating patients with bullous dystrophy complicated by pneumothorax

Our experience in treating patients with bullous dystrophy complicated by pneumothorax. Bullous emphysema of the lung is a local alteration of lung tissue characterized by the destruction of alveolar septa and the formation of air cysts with a diameter of more than 0.5 cm (bullae), the walls of which are lined with alveolar epithelium (with lung tissue density below -860 HU). The aim of the study was to determine effective tactics and select a rational type of surgical intervention in cases of spontaneous pneumothorax where complete lung re-expansion was not achieved through drainage. It was found that men are affected 5-10 times more often than women, predominantly among patients with bronchopulmonary diseases. By draining the pleural cavity, complete lung re-expansion was achieved within 7-10 days in 273 patients (66.3%), within 11-30 days in 16 patients (3.9%), while 123 patients (29.9%) required surgical intervention for full lung re-expansion.

Histology of fetal lungs at different gestational age

The lecture is devoted to the morphological characteristics of the maturation of lung tissue structures in the fetal period. Fetal histology of the lungs presents the intrauterine development of lung tissue in four successive stages: pseudoglandular, canalicular, saccular and alveolar, each has specific morphological criteria. The following morphological features are predetermined: the development of alveolar epithelium, the ratio of mesenchyme towards the area in alveolar spaces, the degree of proliferation and location of vessels of the microcirculatory bed towards prealveolar partitions. During the fetal period the alveolar columnar epithelium is flattened and differentiates into alveolocytes type I and II, the area of the mesenchyme gradually decreases and by the birth of a full-term newborn kid it is present mainly in the thickness between the alveolar septa, microcirculation vessels, initially laying deep in the thickness of the mesenchymal tissue, gradually proliferate, approach the pre-alveolar epithelium, channeling it with the formation of alveolar capillary membranes. Air exchange in the lung tissue is mainly provided with two factors: the presence of second-order alveolocytes capable of producing surfactant, and a sufficient formation of alveoli as well. This work summarizes the basics of fetal lung histology with the demonstration of histological preparations of the lungs at different stages of intrauterine development.

Detection and Quantification of Cryptococcus Uptake by Phagocytic Cells Using Imaging Flow Cytometry.

Cryptococcus neoformans, the predominant etiological agent of cryptococcosis, is an encapsulated fungal pathogen found ubiquitously in the environment that causes pneumonia and life-threatening infections of the central nervous system. Following inhalation of yeasts or desiccated basidiospores into the lung alveoli, resident pulmonary phagocytic cells aid in the identification and eradication of Cryptococcus yeast through their arsenal of pattern recognition receptors (PRRs). PRRs recognize conserved pathogen-associated molecular patterns (PAMPs), such as branched mannans, β-glucans, and chitins that are the major components of the fungal cell wall. However, the key receptors/ligand interactions required for cryptococcal recognition and eventual fungal clearance have yet to be elucidated. Here we present an imaging flow cytometer (IFC) method that offers a novel quantitative cellular imaging and population statistics tool to accurately measure phagocytosis of fungal cells. It has the capacity to measure two distinct steps of phagocytosis: association/attachment and internalization in a high-throughput and quantitative manner that is difficult to achieve with other technologies. Results from these IFC studies allow for the potential to identify PRRs required for recognition, uptake, and subsequent activation of cytokine production, as well as other effector cell responses required for fungal clearance.

Illuminating a bacterial adaptation mechanism: Infrared-driven cell division in deep-sea hydrothermal vent environments

<p>Based on Planck's black-body radiation law, deep-sea hydrothermal vent chimneys emit light, predominantly infrared light, which potentially supports bacterial photosynthesis in this ecosystem independently of the solar energy. To investigate the impact of this geothermal light on bacterial growth, we collected samples from the Southwest Indian Ridge and demonstrated that infrared light alone promotes bacterial growth and alters population composition. The mechanism of infrared stimulated growth was analyzed by monitoring cell wall synthesis using the <i>Tepidibacter hydrothermalis</i> strain SWIR-1, which was isolated from cultures enriched through infrared irradiation. The results showed that the elevated hydrostatic pressure inhibited septal peptidoglycan synthesis and cell division, but had less effect on cell elongation, chromosome replication and segregation. The dominant cell shape was filaments with some swelling and inertness in cell wall synthesis depending on the level of pressure applied. Interestingly, irradiation with 880 nm infrared light effectively initiated septal synthesis and alleviated the obstruction. This revelation uncovers a novel adaptation mechanism involving infrared light for bacteria dwelling in deep-sea environments, and sheds light on the potential of infrared-mediated photobiomodulation.</p>

Menaquinone-4 Alleviates Sepsis-Associated Acute Lung Injury via Activating SIRT3-p53/SLC7A11 Pathway.

Sepsis-associated acute lung injury (SI-ALI) is triggered by various direct or indirect noncardiogenic factors affecting the alveolar epithelium and capillary endothelial cells. Menaquinone-4 (MK-4), a major component of vitamin K, plays a crucial role as an antioxidant by effectively neutralizing reactive oxygen species (ROS) and safeguarding critical biomolecules from oxidative harm within cells. However, the specific mechanisms and clinical implications of MK-4 in SI-ALI are unclear and require further study. Cecal ligation and puncture (CLP) surgery is a commonly used method to induce sepsis in C57BL/6N wild-type mice, and the mice were administered MK-4 at a dosage of 200 mg/kg/day and 3-TYP at 5 mg/kg/day via intraperitoneal injection for 3 days, or erastin (5 mg/kg) 0.5hours before CLP surgery. The mice were sacrificed 24hours after CLP surgery, and blood and lung tissue samples were collected. Pathological changes in the lung tissue and oxidative stress levels were detected. The expression levels of Sirt3, acetylated lysine, p53, SLC7A11 ALOX12 and ferroptosis-related proteins were determined. ligation and puncture (CLP). In this study, we observed that the lung inflammation was associated with reduced Sirt3 expression and increased acetylated lysine levels. The progression of SI-ALI was mitigated by MK-4 through its role in upregulating Sirt3 expression. MK-4 achieved antioxidant effects by downregulating ROS and inflammatory factor levels. Mechanistically, MK-4 inhibited the p53/SLC7A11 signalling pathway in ferroptosis by inhibiting the acetylation of p53, independent of p53 levels. In addition, MK-4 inhibited ferroptosis independent of GPX4. These findings indicate that MK-4 is a promising novel therapeutic agent for treating SI-ALI and possibly sepsis. These experiments revealed that MK-4 acts as a ferroptosis suppressor, increasing the expression of Sirt3, inhibiting the p53/SLC7A11 signalling pathway, and reducing oxidative stress and inflammatory responses, thereby exerting a protective effect against ALI in sepsis.

ОЦЕНКА ПАТОМОРФОЛОГИЧЕСКИХ ИЗМЕНЕНИЙ В ЛЕГКИХ УБОЙНЫХ СВИНЕЙ

The lungs of 12 pigs were studied with the aim to determine morphological changes, caused on a slaughtering with carbon dioxide stunning. Pulmonary alveoli edema and fullness of blood vessels were found. Pathological lesions typical for blood aspiration were not detected. Also veterinary and sanitary standards for meat and animal slaughter products were investigated to find recommendations on lungs utilization with fullness of blood vessels lesions.

Functional role of IL-19 in a mouse model of L-arginine-induced pancreatitis and related lung injury.

IL-19 is a member of IL-10 family and is mainly produced by macrophages. Acute pancreatitis (AP) is an inflammatory disease characterized by acinar cell injury and necrosis. In the present study, the role of IL-19 in AP and AP-associated lung injury in mice was explored using L-arginine-induced pancreatitis. Experimental pancreatitis was induced by intraperitoneal injection of L-arginine in wild-type (WT) and IL-19 gene-deficient (IL-19 KO) mice. Among the mice treated with L-arginine, the serum amylase level was significantly increased in the IL-19 KO mice, and interstitial edema, analyzed using hematoxylin and eosin-stained sections, was aggravated mildly in IL-19 KO mice compared with WT mice. Furthermore, the mRNA expression of tumor necrosis factor-α was significantly upregulated in IL-19 KO mice treated with L-arginine compared with WT mice treated with L-arginine. IL-19 mRNA was equally expressed in the pancreases of both control and L-arginine-treated WT mice. The conditions of lung alveoli were then evaluated in WT and IL-19 KO mice treated with L-arginine. In mice with L-arginine-induced pancreatitis, the alveolar area was remarkedly decreased, and expression of lung myeloperoxidase was significantly increased in IL-19 KO mice compared with WT mice. In the lungs, the mRNA expression of IL-6 and inducible nitric oxide synthase was significantly increased in IL-19 KO mice compared with WT mice. In summary, IL-19 was proposed to alleviate L-arginine-induced pancreatitis by regulating TNF-α production and to protect against AP-related lung injury by inhibiting neutrophil migration.

Liquid air filtration and continuous monitoring: Customized indoor air quality

Air treatment in environmental air conditioning systems exposes the system to gases, contaminants, and often biological pollutants that cannot be solved by traditional mechanical filtration, motivating decision-makers to diagnose challenges and develop innovative strategies to mitigate the problem. More and more, in environments with high turnover of people (e.g., hospitals, hotels and shopping centers), fresh air ventilations are avoided and replaced by closed windows air purifier solutions to account for undesirable saturation of the atmosphere and the presence of pollutants such as PM10, PM2.5, PM1.0, nitrogen, and carbon oxides. The consensus is that polluting gases render the most efficient traditional filters ineffective. The ANSI/ASHRAE 62.1 and EN13779 standards reveal the absence of air treatment technologies that use the wet route in air conditioning systems. This work discusses the liquid air multi-venturi centrifugation technology of hydrodynamic precipitator purifiers in association with the synchronized and continuous monitoring of parameters (PM10, PM2.5, PM1.0, CO2) in the external urban environment and internal environments of a shopping center. It evaluates the performance of the wet route for the physical-chemical and biological treatment of air. Efficiency for retaining particulate matter in a single step without disposable filter reached levels above F9 (85-95% PM2.5), with a reduction of 82.4% for CO2. Wet route technology extends the air conditioner’s life, reducing external air flows and energy consumption by up to 13%, making IAQ a manageable and customizable variable. Among the conclusion of the investigation, the authors believe that the migration of industrial pollutant control technologies, such as liquid filtration promoted by gas scrubbers and hydrodynamic precipitators, should be considered as a first choice option due to the high efficiency achieved in the three types of pollutants to be controlled. That is micrometric particulate matter such as anthropogenic PM1.0 capable of reaching the lung alveoli, chemicals such as carbon dioxide and nitrogen, and biological assets such as viruses and bacteria that showed the vulnerability of HVAC-R systems during the COVID pandemic that rendered windowless corporate buildings unusable.

ДИФФУЗНОЕ АЛЬВЕОЛЯРНОЕ ПОВРЕЖДЕНИЕ ЛЕГКИХ ПРИ COVID-19 В СОЧЕТАНИИ С ДИФФУЗНОЙ В-КРУПНОКЛЕТОЧНОЙ ЛИМФОМОЙ И ИНФАРКТОМ МИОКАРДА. КЛИНИКО-МОРФОЛОГИЧЕСКОЕ НАБЛЮДЕНИЕ

In this article, we report a case of the combination of COVID-19 with diffuse alveolar lung injury and diffuse large B-cell lymphoma with coronary artery compression by tumor nodules in the epicardium, resulting in myocardial infarction and subsequent fatal outcome. The article reviews the complex interaction between COVID-19 and oncological diseases, demonstrating how the coronavirus infection can significantly exacerbate the progression of malignant neoplasms through different mechanisms.

A Case of Lipoid Pneumonia - Hydrocarbon Pneumonitis

Lipoid pneumonia is a rare lung disease that occurs when lipid-containing products are aspirated or inhaled.[1] Exogenous lipoid pneumonia is typically caused by the inhalation or aspiration of animal fats, mineral oils, or vegetable oils, while endogenous lipoid pneumonia occurs due to lipid accumulation within intra-alveolar macrophages in the presence of bronchial obstruction, chronic pulmonary infection, pulmonary alveolar proteinosis, or fat storage diseases.[2] The clinical and radiological features of this condition are non-specific, and a careful history is crucial for accurate diagnosis. Organizing pneumonia can also be observed as a non-specific consequence of interstitial inflammatory diseases such as nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing diffuse alveolar damage, vasculitis, or aspiration pneumonia. In this case report, we discuss the presentation of lipoid pneumonia in a 23-year-old male with a history of petroleum ingestion.

A prospective study on lung parenchymal changes in ingestional poisoning

Abstract Introduction:The ingestion of poison constitutes a critical medical emergency necessitating immediate attention in the emergency department. Respiratory symptoms associated with ingested poisons may manifest through aspiration, cardiopulmonary effects, or direct lung toxicity resulting from alveolar epithelium injury. In the emergency setting, chest imaging, including chest radiographs and CT scans, is commonly employed to assess such symptoms. This study aims to observe and document radiological changes in lung parenchyma among cases of ingestional poisoning admitted to GGH Kakinada. Material and Methods : A prospective observational study was conducted, encompassing cases of ingestional poisoning admitted to GGH Kakinada from January 1st, 2023, to June 1st, 2023. Results: Our findings revealed a predominance of males (71.2%), with the most common age group being 31-40 years (36.6%). Paraquat emerged as the most frequently consumed poison (39.39%). Radiological changes were most prevalent in paraquat poisoning cases (66.67%), and the mortality rate was 39.39%. Conclusion: Paraquat poisoning demonstrates substantial and delayed lung involvement, likely linked to aspiration. All cases resulted in mortality. Early chest X-ray assessment is vital in the emergency department for prompt detection and intervention, anticipating respiratory symptoms in patients with radiological changes.

Human inherited CCR2 deficiency underlies progressive polycystic lung disease

We describe a human lung disease caused by autosomal recessive, complete deficiency of the monocyte chemokine receptor C-C motif chemokine receptor 2 (CCR2). Nine children from five independent kindreds have pulmonary alveolar proteinosis (PAP), progressive polycystic lung disease, and recurrent infections, including bacillus Calmette Guérin (BCG) disease. The CCR2 variants are homozygous in six patients and compound heterozygous in three, and all are loss-of-expression and loss-of-function. They abolish CCR2-agonist chemokine C-C motif ligand 2 (CCL-2)-stimulated Ca2+ signaling in and migration of monocytic cells. All patients have high blood CCL-2 levels, providing a diagnostic test for screening children with unexplained lung or mycobacterial disease. Blood myeloid and lymphoid subsets and interferon (IFN)-γ- and granulocyte-macrophage colony-stimulating factor (GM-CSF)-mediated immunity are unaffected. CCR2-deficient monocytes and alveolar macrophage-like cells have normal gene expression profiles and functions. By contrast, alveolar macrophage counts are about half. Human complete CCR2 deficiency is a genetic etiology of PAP, polycystic lung disease, and recurrent infections caused by impaired CCL2-dependent monocyte migration to the lungs and infected tissues.

Bronkopnömonili Köpeklerde Mycoplasma spp., Streptococcus spp., Bordetella bronchiseptica, Klebsiella spp. ’nin Real-time PCR ve Patolojik Yöntemler ile Teşhisi

There are many bacterial factors that cause respiratory diseases in dogs. Bacterial bronchopneumonia is a lung disease caused by bacteria in the lower respiratory tract and lung parenchyma. In this study, it was aimed to determine Mycoplasma spp., Streptococcus spp., Bordetella bronchiseptica, Klebsiella spp., in dogs with bronchopneumonia by Real-time PCR and to compare the histopathological findings determined according to the agents. The material of the study consisted of lung paraffin blocks of 37 dogs that died due to different reasons and were found to have bronchopneumonia in microscopic examination. Microscopically, edema in the alveolar lumens, shedding of the alveolar epithelium, shedding of the bronch and bronchial epithelium and bronchiectasis, mononuclear cell infiltration (MCI) and Polymorphonuclear leukocytes (PMNL) infiltration in the bronchial lumens, peribronchiolar MCI infiltration, Bacterial clusters localized to the bronch epithelium, PMNL infiltration in the interstitium, multifocal necrosis areas, bleeding and pleuritis were observed. Real-time PCR analysis revealed Bordetella bronchiseptica in 18 (48.64%) cases, Mycoplasma spp. in 9 (24.32%) cases, Streptococcus spp. in 10 (27.02%) cases, and Klebsiella spp. in 2 (5.4%) cases. In conclusion, this study showed that the causative agent can be determined in bacterial bronchopneumonias of dogs with Real-time PCR even in tissues without culture opportunity. In addition, this study indicates that polymicrobial lower respiratory tract infections can also be seen in dogs and reveals that more than one bacterial species should be investigated for diagnosis.