Adjacent Alveoli Research Articles

Acute Gastroenteritis and Bronchopneumonia in an incompletely Immunized Infant – Case Report

Acute gastroenteritis (GEA) is gastrointestinal disease whose signs and symptomps are diarrhea, anorexia, vomiting, abdominal pain and fever. This condition is very common in children. Bronchopneumonia is a patchy inflammation of the lungs (exceeding one or two lobes) where exudate from white blood cells accumulates in the bronchi and bronchioles with spread to adjacent alveoli. Immunization can reduce the risk of the two diseases. This study will comprehensively discuss the relationship between incomplete immunization and the occurrence of ARI and bronchopneumonia in order to enable appropriate management. The method involves conducting a literature review by gathering literature from books and articles published in the last 10 years. We report a case of GEA along with bronchopneumonia in an infant aged 4 months 26 days with a history of incomplete immunization. Catch-up immunization should be carried out in all babies with a history of incomplete immunization to reduce the risk and severity of subsequent.

The UIP/IPF fibroblastic focus is a collagen biosynthesis factory embedded in a distinct extracellular matrix.

Usual interstitial pneumonia (UIP) is a histological pattern characteristic of idiopathic pulmonary fibrosis (IPF). The UIP pattern is patchy with histologically normal lung adjacent to dense fibrotic tissue. At this interface, fibroblastic foci (FF) are present and are sites where myofibroblasts and extracellular matrix (ECM) accumulate. Utilizing laser capture microdissection-coupled mass spectrometry, we interrogated the FF, adjacent mature scar, and adjacent alveoli in 6 fibrotic (UIP/IPF) specimens plus 6 nonfibrotic alveolar specimens as controls. The data were subjected to qualitative and quantitative analysis and histologically validated. We found that the fibrotic alveoli protein signature is defined by immune deregulation as the strongest category. The fibrotic mature scar classified as end-stage fibrosis whereas the FF contained an overabundance of a distinctive ECM compared with the nonfibrotic control. Furthermore, FF were positive for both TGFB1 and TGFB3, whereas the aberrant basaloid cell lining of FF was predominantly positive for TGFB2. In conclusion, spatial proteomics demonstrated distinct protein compositions in the histologically defined regions of UIP/IPF tissue. These data revealed that FF are the main site of collagen biosynthesis and that the adjacent alveoli are abnormal. This essential information will inform future mechanistic studies on fibrosis progression.

Effects of airway deformation and alveolar pores on particle deposition in the lungs

The distal lung (G14–G23), which are composed of alveoli and bronchi, are responsible for almost all gas exchange and micro- and nanoparticle deposition in the lungs. In the existing research using computational fluid dynamics, the geometric modeling accuracy of the bronchial bifurcation structure is given priority, and then the alveoli are attached to bronchi as discrete spherical crowns. This method ignores the correlation between alveoli. In fact, the alveoli have a tessellated distribution, and adjacent alveoli are connected by several alveolar pores. Due to the huge number of alveoli, this seemingly small difference will be greatly amplified, which may lead to a large deviation in the prediction of the overall flow. Accordingly, the objective of this study is to construct a two-dimensional distal lung model including the bronchi, acini, and alveolar pores by using the methods of regular hexagonal tessellational subdivision, fusion, and coordinate transformation. A moving boundary is introduced to simulate the process of airflow and particle deposition in the distal lung, and the effects of bronchial deformation, respiratory frequency, and alveolar pores are obtained. The results show that there are significant differences in intrapulmonary flow patterns with and without alveolar pores. Alveolar pores can establish bypass ventilation downstream of a blockage, thus providing a pathway for particles to enter the airways downstream of the blockage. Changing the respiratory frequency and the amplitude of bronchial deformation will change the relative velocity between particles and moving wall, which, in turn, will change the particle deposition efficiency in the distal lung. To summarize this study, a geometric modeling method for the distal lung with alveolar pores is established, and the important roles of detailed characteristics of the distal lung are revealed. The findings of this study provide a reasonable hydrodynamic mechanism for the prevention of related respiratory diseases.

Bronchoscopy and Lung Fine-Needle Aspiration for Antemortem Evaluation of Pulmonary Involvement in Dogs with Naturally Occurring Canine Leishmaniosis.

Clinical manifestations from the lower respiratory tract are rare in canine leishmaniosis (CanL), making bronchoscopy and lung fine-needle aspiration (FNA) seldomly justified. The aim of this prospective study was to investigate the involvement of Leishmania infantum in the lungs of dogs with naturally occurring CanL by bronchoscopy and examination of bronchoalveolar lavage fluid (BALF), bronchial mucosa biopsies, and FNA, using immunodiagnostics. Dogs with relevant concurrent diseases and azotemia were excluded. Cough was detected in 5/31 (16.1%) dogs. Lesions (hyperemia, edema, mucosal granularity, secretions) were identified upon bronchoscopy in 19/31 (61.3%) dogs. The cytology of BALF revealed histiocytic inflammation in 14/31 (45.2%) dogs; the parasite was identified in one dog (3.2%). The immunofluorescence antibody test in BALF was positive in 15/31 (48.4%) dogs. Histopathology of bronchial mucosa and/or adjacent alveoli revealed lesions (mononuclear cell infiltration, fibrosis, edema, thickening of the inter-alveolar septa) in 24/31 (77.4%) dogs, with no Leishmania amastigotes. Positive antigen staining was observed within the cytoplasm of mononuclear cells in immunocytochemistry and immunohistochemistry. Μononuclear cells showed antigenic positivity in bronchial mucosa (27/31; 87.1%), BALF (30/31; 96.8%), and lung FNA (27/31; 87.1%). In conclusion, lungs seem to be affected from CanL more commonly than previously believed, and bronchoscopy allows obtaining valuable samples for antemortem diagnosis.

Repetitive Ozone Exposures and Evaluation of Pulmonary Inflammation and Remodeling in Diabetic Mouse Strains.

Background:Epidemiological studies support the hypothesis that diabetes alters pulmonary responses to air pollutants like ozone (). The mechanism(s) underlying these associations and potential links among diabetes, , and lung inflammation and remodeling are currently unknown.Objectives:The goal was to determine whether pulmonary responses to repetitive ozone exposures are exacerbated in murine strains that are hyperglycemic and insulin resistant.Methods:Normoglycemic and insulin-sensitive C57BL/6J mice; hyperglycemic, but mildly insulin-resistant, KK mice; and hyperglycemic and markedly insulin-resistant KKAy mice were used for ozone exposure studies. All animals were exposed to filtered air (FA) or repetitive ozone ( , 4 h/d, for 13 consecutive weekdays). Tissue analysis was performed 24 h following the final exposure. This analysis included bronchoalveolar lavage (BAL) for cell and fluid analysis, and tissue for pathology, immunohistology, mRNA, and hydroxyproline.Results:Following repetitive exposure, higher bronchoalveolar lavage fluid inflammatory cells were observed in all mice (), with a notable influx of neutrophils and eosinophils in KK and KKAy mice. Although the lungs of -exposed C57BL/6J and KK mice had minimal centriacinar histological changes without fibrosis, the lungs of -exposed KKAy mice contained marked epithelial hyperplasia in proximal alveolar ducts and adjacent alveoli with associated centriacinar fibrosis. Fibrosis in -exposed KKAy lungs was confirmed with immunohistochemistry, tissue hydroxyproline content, and tissue mRNA expression of fibrosis-associated genes (Ccl11, Il13, and Mmp12). Immunofluorescence staining and confocal microscopy revealed alterations in the structure and composition of the airway and alveolar epithelium in regions of fibrosis.Discussion:Our results demonstrate that in diabetic animal strains repetitive ambient ozone exposure led to early and exaggerated pulmonary inflammation and remodeling. Changes in distal and interstitial airspaces and the activation of Th2 inflammatory and profibrotic pathways in experimental animals provide a preliminary, mechanistic framework to support the emerging epidemiological associations among air pollution, diabetes, and lung disease. https://doi.org/10.1289/EHP7255

Ameliorative effects of Panax ginseng on lung of Lambada cyhalotherin-intoxicated rats

Introduction: Lambada-cyhalotherin (LCT) caused severe oxidative damage in liver, lung and testis.Aim of the Study: The objective of this research was to evaluate the ameliorative activity and underlying techniques of pure Panax ginseng (G) using rat model of LCT-induced lung damage.Materials and Methods: 36 male adult laboratory rats Rattus norvegicus domestica in weights around 135±10 g were separated into 6 experimental groups: 1st control group. 2nd and 3th groups were G groups (100 and 200 mg G/kg b. wt.) LCT group was given by oral gavage LCT (61.2 mg /kg b. wt.) that is equivalent to 1/10 of LD50. The 5th and 6th groups were co-treated with two doses of G.Results: LCT significantly decreased superoxide dismutase (SOD), catalase (CAT) and total thiol (T. thiol) and increased lipid peroxidation (LPO). mRNA and protein expression levels of p53 gene (apoptotic gene) were increased, whereas, Bcl-2 gene (anti-apoptotic gene) mRNA and protein expression levels were decreased in LCT-treated animals. Also, light microscopic and ultrastructure studies for lung tissues of LCT-treated animals showed marked hyperplasia of dilated bronchioles wall, RBCs extravasation in bronchiolium lumen and mononuclear leukocytic infiltration in parenchyma. Additionally, blood vessels congested with thickened walls, alveoli appeared collapsed with compensatory expansion of adjacent alveoli divided by thickened inter-alveolar septa, besides to damage in type 1 and type 2 pneumocytes. G co-treatment attenuated oxidative stress biomarkers. Both tested doses of G significantly decreased p53 and elevate Bcl-2 mRNA and protein expression levels and revealed significant amelioration and restoration of normal histology and ultrastructure of lung.Conclusion: In summary, G has exhibited ameliorative activity against oxidative stress induced by LCT in lung, apoptosis, histopathological and ultrastructural changes in albino rats.

Optical Determination of Age‐Related Changes in Subpleural Collagen of Live Human Lungs

The impact of age on lung physiology is not known. Collagen is an important determinant of lung structure and function. Therefore, age‐related changes in collagen quantity, geometry and structure can lead to changes in lung function. CT scans of asymptomatic patients reveal age‐dependent increase of subpleural radiologic densities, called interstitial lung abnormalities (ILAs) that predispose to pulmonary fibrosis. However it is not known whether ILAs are collagen deposits that impair alveolar function. Since real‐time fluorescence microscopy (RFI) of the human lung has not been done, we carried out two‐photon and confocal microscopy (2P‐CF) of live, transplant‐reject lungs to determine the age‐related profile of subpleural collagen density (SCD) and whether this affects surfactant secretion. For RFI, we cannulated the bronchus and the artery of the lingular lobe to enable inflation and perfusion. Then, we held the lobe at constant alveolar pressure of 5 cmH2O. To stain alveolar epithelial cells, we subpleurally injected fluorescent dyes by means of a 31‐gauge needle. We detected subpleural collagen as the fluorescence of second harmonics generation (SHG). We quantified subpleural collagen density (SCD) as the integrated collagen fluorescence occurring in the space between the visceral pleura and the alveolar epithelium. To determine surfactant secretion, we quantified the timed appearance of lipid‐sensitive fluorescence in the alveolar space following a transient hyperinflation of the lingular lobe. Our data show that subpleural collagen was evident as well‐defined and evenly spaced cables in young lungs (median age 37 years). By contrast, subpleural collagen in aged lungs (median age 63 years) was marked by poorly formed cables surrounded by diffuse SHG fluorescence. We show that SCDs varied in different regions in all lungs and that SCD was significantly higher in aged than young lungs. Further, in high SCD regions, hyperinflation‐induced alveolar expansion and surfactant secretion were abrogated (p<0.05). Thus, SCDs increase with age and negatively regulate surfactant secretion from adjacent alveoli. SCDs may correspond to ILAs. Our findings raise the novel possibility that a risk‐factor in development of pulmonary fibrosis might be the disruption of alveolar homeostasis caused by age‐related changes in subpleural collagen (HL145547, HL36024).Support or Funding InformationHL145547, HL36024

The Distribution of Collagen and Elastic Fibres in the Lactating Bovine Mammary Gland

Abstract Collagen and elastic fibres are generally present in organs whose normal function requires great resistance and elasticity. The aim of this study was to localize the collagen and elastic fibres in the stroma of the bovine lactating mammary gland and to determine their role in the process of milk ejection. For this purpose, the histochemical staining for collagen and the immunohistochemical method for the detection of elastin were used. The accumulation of scattered collagen fibres was observed between and inside the lobules where they formed distinct septa. Between secretory alveoli, the collagen fibres were found to be concentrated into two incomplete layers surrounding the blood capillaries. Bundles of elastic fibres in high density were located in the interlobular spaces. A dense network of elastic fibres was located between adjacent alveoli. Elastic membranes were located beneath the secretory epithelium. The high concentration of the collagen and elastic fibres indicated, that both types of fibres play a significant role in the resistance during the secretory stage and in the recoil of the mammary gland after milk ejection.

Dynamic susceptibility contrast 19 F-MRI of inhaled perfluoropropane: a novel approach to combined pulmonary ventilation and perfusion imaging.

PurposeTo assess alveolar perfusion by applying dynamic susceptibility contrast MRI to 19F‐MRI of inhaled perfluoropropane (PFP). We hypothesized that passage of gadolinium‐based contrast agent (GBCA) through the pulmonary microvasculature would reduce magnetic susceptibility differences between water and gas components of the lung, elevating the T2∗ of PFP.MethodsLung‐representative phantoms were constructed of aqueous PFP‐filled foams to characterize the impact of aqueous/gas phase magnetic susceptibility differences on PFP T2∗. Aqueous phase magnetic susceptibility was modulated by addition of different concentrations of GBCA. In vivo studies were performed to measure the impact of intravenously administered GBCA on the T2∗ of inhaled PFP in mice (7.0 Tesla) and in healthy volunteers (3.0 Tesla).ResultsPerfluoropropane T2∗ was sensitive to modulation of magnetic susceptibility difference between gas and water components of the lung, both in phantom models and in vivo. Negation of aqueous/gas phase magnetic susceptibility difference was achieved in lung‐representative phantoms and in mice, resulting in a ~2 to 3× elevation in PFP T2∗ (3.7 to 8.5 ms and 0.7 to 2.6 ms, respectively). Human studies demonstrated a transient elevation of inhaled PFP T2∗ (1.50 to 1.64 ms) during passage of GBCA bolus through the lung circulation, demonstrating sensitivity to lung perfusion.ConclusionWe demonstrate indirect detection of a GBCA in the pulmonary microvasculature via changes to the T2∗ of gas phase PFP within directly adjacent alveoli. This approach holds potential for assessing alveolar perfusion by dynamic susceptibility contrast 19F‐MRI of inhaled PFP, with concurrent assessment of lung ventilation properties, relevant to lung physiology and disease.

ErbB3 Ligand Heregulin1 Is a Major Mitogenic Factor for Uncontrolled Lung Cancer Cell Proliferation

There are seven ligands for the epidermal growth factor receptor (EGFR) ErbB1 and two ligands for ErbB3. EGFR can form a homodimer or a heterodimer with ErbB3. In this study, we investigated whether homodimers or heterodimers, and which ligand, play a major role in cancer development, with the goal of ultimately identifying therapeutic targets. We demonstrated that the ErbB3 ligand heregulin1 is the strongest mitogenic factor for non–small cell lung cancer cells and is more potent in activating EGFRmut-ErbB3 heterodimers than EGFRwt-ErbB3 heterodimers. We discovered that four of the seven EGFR ligands inhibited heregulin1-induced EGFRwt-ErbB3 activation and cell proliferation by promoting dephosphorylation of heregulin1-induced ErbB3 phosphorylation, whereas the other three did not exhibit such inhibition. Importantly, those four EGFR ligands did not inhibit heregulin1-induced EGFRmut-ErbB3 activation and proliferation of cells with EGFR mutants. We demonstrated that ErbB3 was overexpressed in the lung cancer cells but not in the adjacent normal alveoli or stromal tissue. EGFR and heregulin1 were also highly expressed in lung cancer cells. We conclude that the overexpression of heregulin1, ErbB3, and EGFR mutant renders uncontrolled cell proliferation.

IL-9 exacerbates the development of chronic obstructive pulmonary disease through oxidative stress.

To investigate the role of IL-9 in chronic obstructive pulmonary disease (COPD), and to explore its potential mechanism. A mouse COPD model was established by exposure to cigarette smoke. COPD mice were then randomly assigned into two groups, including: the PBS group and the IL-9 antibody group. The above two groups were treated with phosphate-buffered saline (PBS) or IL-9 injection, respectively. The histopathological changes in lung tissues of mice were observed by hematoxylin-eosin (H&E) staining. Immunohistochemistry was performed to detect IL-9-positive (IL-9+) cells in lung tissues. Expression levels of IL-9, sIL-9R, STAT3, and p-STAT3 in peripheral blood of mice were determined by quantitative Real time-polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and Western blot, respectively. In addition, the expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) were detected. H&E staining results showed that the airway wall structure of COPD mice in the PBS group was irregular. Ciliated columnar epithelium exhibited marked degeneration, necrosis and shedding. Besides, numerous inflammatory cell infiltration, narrowing and rupture of the alveolar septa, and larger cysts fused by adjacent alveoli were observed. H&E staining also indicated that the structure of alveolar epithelium was severely impaired in COPD mice. However, the pathological changes in lung tissues of mice in the IL-9 antibody group were much milder than those of the PBS group. Immunohistochemistry results showed a significant deposition of IL-9+ cells in the lung tissues of the PBS group. Meanwhile, the mRNA and protein levels of IL-9, sIL-9R, and p-STAT3 in the PBS group were also remarkably higher than those of the IL-9 antibody group. In addition, SOD content in the PBS group was significantly decreased, whereas the levels of MDA and ROS were significantly increased than those of the IL-9 antibody group. IL-9 activated STAT3 and aggravated lung injury in COPD mice by increasing inflammatory and oxidative stress.

Toll-Like Receptor 4 (TLR-4) Pathway Promotes Pulmonary Inflammation in Chronic Intermittent Hypoxia-Induced Obstructive Sleep Apnea.

BackgroundStudies have shown that intermittent hypoxia mimics obstructive sleep apnea in causing pulmonary inflammation, but the mechanism is not yet clear.TLR-4 is a recognized proinflammatory factor, so the purpose of this study was to assess the function of TLR-4 in pulmonary inflammation induced by chronic intermittent hypoxia simulating obstructive sleep apnea.Material/MethodsHealthy male Wistar rats were divided into 3 groups (8 in each group): the normoxia control group (CG), the intermittent hypoxia group (IH), and the TLR4 antagonist TAK242 treatment group (3 mg/kg, daily), with exposure durations of 12 weeks and 16 weeks (HI). The morphological changes of lung tissue were determined with hematoxylin-eosin (HE) staining. The expressions of the TLR-4 pathway in lung tissue were tested by Western blotting and RT-PCR. The levels of IL-6 and TNF-α in serum and lung tissue were detected by enzyme-linked immunosorbent assay (ELISA). The levels of SOD and MDA in lung tissue were detected by use of SOD and MDA kits, respectively.ResultsAfter TAK242 treatment, damage to lung tissue was increased, and the expressions of TLR-4, MYD88, P65, IL-6, TNF-α, MDA, and SOD were decreased. Intermittent hypoxic exposure caused alveolar expansion, thickening of alveolar septum, and fusion of adjacent alveoli into larger cysts under intermittent hypoxia in a time-dependent manner. Compared with the CG and HI groups, the mean lining interval (MLI) become more thickened and the alveolar destruction index (DI) increased significantly in the IH group.ConclusionsChronic intermittent hypoxia causes pulmonary inflammatory response and the inflammatory pathway involved in TLR4 receptor may be one of the mechanisms that trigger lung inflammation.

IL-33 induced inflammation exacerbated the development of chronic obstructive pulmonary disease through oxidative stress.

We aimed at exploring the role of IL-33 in mouse chronic obstructive pulmonary disease and its potential molecular mechanism. The chronic obstructive pulmonary disease (COPD) mice model was established by cigarette smoking (CS). COPD mice were randomly assigned into PBS group and IL-33 antibody group. The peripheral blood and lung tissues of mice from two groups were collected for the following experiments. Pathological changes of the lung tissues in both groups were analyzed by hematoxylin and eosin (HE) staining. IL-33 positive cells in lung tissues were detected by immunohistochemistry. Then, the mRNA and protein levels of IL-33, sST2, ERK and TNF-α in the mice peripheral blood of the two groups were accessed by Real-time polymerasechainreaction (RT-PCR) and Western blot. Finally, the indicators related to oxidative stress, including superoxide dismutase (SOD), malondialdehyde (MDA) and reactive oxygen species (ROS) in the mice serum of two groups were measured. After successful construction of COPD mouse model by CS, HE staining illustrated that the structure of airway wall of lung tissue in mice from PBS group was irregular. The ciliated columnar epithelium presented significant degeneration, necrosis and shedding. A large amount of inflammation cell infiltration was observed in vascular tissues. The alveolar epithelial structure was severely damaged and alveolar septum was narrowed and ruptured. Adjacent alveoli were found to be fused into larger cysts. The above pathological changes were relatively better in mice from IL-33 antibody group. Immunohistochemical results demonstrated that IL-33 was remarkably deposited in the lung tissue of PBS group. The mRNA and protein levels of IL-33, sST2, ERK and TNF-α in peripheral blood of PBS group were much higher than those of IL-33 antibody group. At the same time, SOD level in PBS group decreased, while MDA level and ROS production increased. IL-33 aggravates lung injury in COPD mice by increasing inflammation response and oxidative stress, which may serve as a target for predicting and treating COPD.

Diagnosis of Respiratory Bronchiolitis associated interstitial lung disease

Respiratory Bronchiolitis (RB), described by Niewoehner et al in 1974, is a common finding in heavy smokers and is characterised by the presence of pigmented macrophages within respiratory bronchioles and adjacent alveoli. In the 1980s, Myers et al described RB associated with interstitial lung disease (RBILD), which is a rare entity expressed as an amplified respiratory bronchiolitis in response to cigarette smoke. The authors studied a group of 8 patients with biopsy-proven RBILD diagnosed within the last five years, and assessed epidemiological data, clinical and imaging features, lung function tests, bronchoalveolar lavage findings, therapeutic approaches and clinical evolution. The most difficult differential diagnosis is between RBILD and Desquamative Interstitial Pneumonia (DIP), which seems to suggest that these disorders are either end of the same spectrum, although the authors claim that there are some clinical, morphological and prognostic distinctions. The diagnosis of RBILD requires an appropriate clinical setting (including smoking habits), characteristic image findings (like ground glass shadowing and centrilobular nodules), and Bronchoalveolar Lavage (BAL) data to exclude other diagnosis. Pathological confirmation may also be important, not only to exclude more adverse interstitial lung disease, such as idiopathic pulmonary fibrosis, but also, as in the eight cases presented, to illustrate some specific features such as the prevalence of lymphocytosis in BAL.

The "Tree-in-Bud" Pattern on Chest CT: Radiologic and Microbiologic Correlation.

Tree-in-bud (TIB) is a radiologic pattern seen on high-resolution chest CT reflecting bronchiolar mucoid impaction occasionally with additional involvement of adjacent alveoli. Its microbiologic significance has not been systematically evaluated. We aimed to establish the incidence of the TIB pattern as a proportion of all patients undergoing chest CT and to identify its etiology wherever possible. We included all patients with TIB pattern detected on chest CT in our institution from January 2007 to June 2012 and correlated this radiologic finding to the microbiologic etiology, which were available, for each patient. During the study period, TIB pattern was described in 326 patients, which is 1.8% of all chest CTs. Of these, 220 (67.5%) patients had an infectious etiology and 34 (10.4%) had aspiration pneumonia. Other presumptive etiologies were in 13 (4%) lung malignancy, 31 (9.5%) other malignancies, 20 cases (6%) inconclusive etiology or incidental findings, and 8 (2.5%) had other inflammatory disorders. The relative incidence of the various organisms isolated reflected the overall incidence of these bacteria in community- or hospital-acquired populations independent of the TIB pattern. No correlation was found between distribution of TIB, the immune status, and the organism isolated. TIB pattern reflects endobronchiolar inflammation due mainly but not exclusively to an infectious cause. The microbiologic etiology in patients with this finding is similar to that of the general population (community acquired versus hospital acquired).

Toward a comprehensive interpretation of intravital microscopy images in studies of lung tissue dynamics.

Intravital microscopy (IVM) is a well-established imaging technique for real-time monitoring of microscale lung tissue dynamics. Although accepted as a gold standard in respiratory research, its characteristic image features are scarcely understood, especially when trying to determine the actual position of alveolar walls. To allow correct interpretation of these images with respect to the true geometry of the lung parenchyma, we analyzed IVM data of alveoli in a mouse model in comparison with simultaneously acquired optical coherence tomography images. Several IVM characteristics, such as double ring structures or disappearing alveoli in regions of liquid filling, could be identified and related to the position of alveoli relative to each other. Utilizing a ray tracing approach based on an idealized geometry of the mouse lung parenchyma, two major reflection processes could be attributed to the IVM image formation: partial reflection and total internal reflection between adjacent alveoli. Considering the origin of the reflexes, a model was developed to determine the true position of alveolar walls within IVM images. These results allow thorough understanding of IVM data and may serve as a basis for the correction of alveolar sizes for more accurate quantitative analysis within future studies of lung tissue dynamics.

Histological alteration of the pulmonary alveoli, renal cortex and spleen following exposure to open refuse dump site

Background: Wastes are mainly unwanted products from domestic and industrial sources, which increases due to accelerated industrialization, urbanization, and population growth. Open refuse dumping is the predominant form of waste disposal method in Nigeria and presents huge environmental and health challenges. Hence, this study investigated the effects of long-term exposure of rats to refuse dump sites on histological and serum analysis in three organs; kidney, lungs, and spleen. Materials and Methods: Twelve Wistar rats of both sexes were divided into two groups made up of 6 rats in each group. Group A was the controls and group B was the experimental. The experimental rats were exposed to refuse dump fume by keeping them in a research hut built in a refuse dump site for 8 months while the control rats were keep in the Department of Human Anatomy, Niger Delta University, Wilberforce Island, Bayelsa State. Results: There was loss of the elastic tissue support for bronchioles, alveolar wall and coalescence of adjacent alveoli as compared with the control. Serum urea concentrations were significantly increased (P < 0.05) in exposed rats (9.08 ± 1.58) compared with control rats (5.00 ± 0.32). Similarly, serum creatinine concentrations were significantly increased (P < 0.05) in exposed rats (106.20 ± 14.94) compared to Control rats (53.67 ± 5.68). All measured serum electrolytes were significantly altered (P < 0.05). Sodium ions (Na+) (90.17 ± 7.68) and bicarbonate ions (HCO3−) (2.33 ± 0.33) were significantly reduced (P < 0.05) while potassium ions (K+) (61.83 ± 6.70) and chloride ions (Cl−) (117.2 ± 3.08) were significantly increased (P < 0.05). Conclusion: Our results revealed histological distortion in experimental animals due to exposure to refuse dump site.

Intraepithelial T-cell cytotoxicity, induced bronchus-associated lymphoid tissue, and proliferation of pneumocytes in experimental mouse models of influenza.

Immunopathologic examination of the lungs of mice with experimental influenza virus infection reveals three prominent findings. (i) There is rapidly developing perivascular (arterial) and peribronchial infiltration with T-cells and invasion of T-cells into the bronchiolar epithelium, separation of epithelial cells from each other and from the basement membrane, leading to defoliation of the bronchial epithelium. This reaction is analogous to a viral exanthema of the skin, such as measles and smallpox. This previously described but unappreciated reaction most likely is an effective way to eliminate virus-infected cells, but may contribute to acute toxicity and mortality. (ii) After this, there is formation of dense collections of lymphocytes adjacent to bronchi consisting mainly of B-cells, with a scattering of T-cells and macrophages. This is known as induced bronchial-associated lymphoid tissue (iBALT) and correlates with increased interleukin (IL)-17 in the lung. iBALT provides sites for a local immune reaction in the lung to both the original infection and related viral infections (heterologous immunity). (iii) Within the first 2-3 weeks, there is proliferation of type II pneumocytes and/or terminal bronchial epithelial cells extending from the terminal bronchioles into the adjacent alveoli, eventually leading to large zones of the lung filled with tumor-like epithelial cells with squamous metaplasia. The proliferation correlates with IL-17 and IL-22 expression, and the extent of this reaction appears to be determined by the availability of T-regulatory cells.

Reply to Perlman.

Letters to the EditorReply to PerlmanZhenglong ChenZhenglong ChenBiomedical Instrument Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China; and Department of Precise Medical Device, Shanghai Medical Instrumentation College, Shanghai, ChinaPublished Online:15 Oct 2014https://doi.org/10.1152/japplphysiol.00734.2014MoreSectionsPDF (28 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations to the editor: We have paid close attention to the new advances in pulmonary mechanics from Dr. Perlman's group and herein thank Dr. Perlman for her interest in our model (3). Dr. Perlman believes that surface tension between adjacent alveoli tends to be equal due to diffusion and Maranongi effects and she further poses recent experimental evidence supporting her argument. But this is true only under the following two conditions: 1) the connected two alveoli share a common alveolar duct and 2) at high ventilation frequency. Dr. Perlman overlooks the additional situation in which the two adjacent alveoli share different alveolar ducts and/or their alveolar mouths are blocked by liquid plug. In this case, surface tension between two alveoli might well be different. Moreover, even for two adjacent and connected alveoli, the distribution of surface tension depends on ventilation frequency. Low ventilation frequency provides a nonuniform surfactant distribution (1).In responding to the contention “only in an excised lung that has been degassed and reinflated with liquid can surface tension be zero,” what Dr. Perlman could again fail to consider is the case in which the airways leading to flooded alveoli are completely collapsed (2) so that these alveoli are disconnected with air-liquid interface and, therefore, surface tension equals zero. We highly acknowledge Dr. Perlman for pointing out that Fig.6 is an optical section above the height of the meniscus present in the alveolus. But on the other hand, it was from this representative image that we had the idea to perform the third simulation. In fact, if we admit the aforementioned situation, namely zero surface tension, is possible, this image we think can be used to support our conclusion—when one alveolus is completely flooded, the septum shared by its aerated neighbor would bulge into the flooded alveolus. Because a cross section of such two adjoining alveoli is exactly the same as Fig.6.Dr. Perlman is correct in pointing out that the inconsistent use of λ will introduce an error; however, only if we take L0 in Eq. 1 as the value of known unstressed length as in Eq. 11, are we able to eliminate this error. We agree that a more accurate relation between Palv and Rb contributes to enhance credibility of our results. This is also the future direction. We disagree with Dr. Perlman on the third point. As we stated at the beginning of results, we obtained the length of SS' by trial and error without assuming it increases proportionately with aerated alveolar walls. Actually, our simulation showed that if assuming SS' proportionate increase then the calculated aerated alveolar geometries in cases 1 and 2 were identical, with constant angle SOS' = 60°, which was apparently irreconcilable with the truth.The present model is just a preliminary step in building a systematically theoretical framework to quantify lung injury. In this regard, a practical model should be able to estimate not only tension stress but shear stress with reporting confidence limits, as suggested by Dr. Perlman.DISCLOSURESNo conflicts of interest, financial or otherwise, are declared by the author(s).AUTHOR CONTRIBUTIONSAuthor contributions: Z.-L.C. drafted manuscript.REFERENCES1. Anderson JC, Molthen RC, Dawson CA, Haworth ST, Bull JL, Glucksberg MR, Grotberg JB. Effect of ventilation rate on instilled surfactant distribution in the pulmonary airways of rats. J Appl Physiol 97: 45–56, 2004.Link | ISI | Google Scholar2. Ghadiali SN, Gaver DP. Biomechanics of liquid-epithelium interactions in pulmonary airways. Respir Physiol Neurobiol 163: 232–243, 2008.Crossref | PubMed | ISI | Google Scholar3. Perlman CE. On modeling edematous alveolar mechanics. J Appl Physiol; doi:10.1152/japplphysiol.00696.2014.Link | ISI | Google ScholarAUTHOR NOTESAddress for reprint requests and other correspondence: Z. Chen, Biomedical Instrument Institute, School of Biomedical Engineering, Shanghai Jiao Tong Univ., Shanghai, China (e-mail: [email protected]com). Download PDF Previous Back to Top Next FiguresReferencesRelatedInformation Related ArticlesOn modeling edematous alveolar mechanics 15 Oct 2014Journal of Applied Physiology More from this issue > Volume 117Issue 8October 2014Pages 938-938 Copyright & PermissionsCopyright © 2014 the American Physiological Societyhttps://doi.org/10.1152/japplphysiol.00734.2014PubMed25318932History Published online 15 October 2014 Published in print 15 October 2014 Metrics

Closely Related Influenza Viruses Induce Contrasting Respiratory Tract Immunopathology

The swine-origin H1N1 virus which emerged in 2009 resulted in the first influenza pandemic of the 21st century. Although the majority of infections were moderate, a significant proportion of infections were severe and characterized by acute respiratory distress syndrome and pulmonary edema. We compared two isolates from the 2009 H1N1 pandemic; A/California/07/09 (CA/07) and A/Netherlands/602/09 (NL/602) viruses that share greater than 99% sequence identity. Though genetically similar, these viruses exhibit contrasting pathological effects. Mice that were infected with 800 plaque forming unit (PFU) of CA/07 virus rapidly lost weight, which was concurrent with detection of high pulmonary concentrations of MCP-1, MIG, IP-10 and TIMP-1. Initially, severe bronchiolar epithelial necrosis and acute respiratory distress was observed, followed by marked bronchiolar epithelial hyperplasia. Mononuclear cell infiltration was initially localized to perivascular and peribronchiolar interstitium and then spread to adjacent alveoli. Infiltrating cells were phenotypically CD11bhi, F4/80lo. In contrast, when mice were infected with 800 PFU of NL/602 virus, minimal weight loss was observed, and concentrations of cytokines in the lung were significantly lower. Inflammation was primarily restricted to the bronchioles and perivascular interstitium with minimal spread to alveoli. Infiltrating cells include foamy macrophages and surface markers were characterized as CD11blo/-, F4/80hi. These two genetically similar viruses can be useful strains with which to investigate immune-regulatory determinants of pathogenesis of influenza virus.