Alveolar Septal Inflammation Research Articles

Atoll sign ieventail diagnostic

The atoll sign or inverted halot sign is seen on high-resolution chest CT scans as a central frosted glass area surrounded by peripheral condensation in a ring or crescent, the contours of which may be smooth or spiculated [1]. Histologically, the central zone (ground glass opacity) corresponds to alveolar septal inflammation and cellular debris in the alveolar spaces, while the condensed peripheral zone corresponds to granulomatous tissue in the distal air spaces [2]

Eicosapentaenoic acid potentiates the therapeutic effects of adipose tissue-derived mesenchymal stromal cells on lung and distal organ injury in experimental sepsis

BackgroundEven though mesenchymal stromal cells (MSCs) mitigate lung and distal organ damage in experimental polymicrobial sepsis, mortality remains high. We investigated whether preconditioning with eicosapentaenoic acid (EPA) would potentiate MSC actions in experimental sepsis by further decreasing lung and distal organ injury, thereby improving survival.MethodsIn C57BL/6 mice, sepsis was induced by cecal hligation and puncture (CLP); sham-operated animals were used as control. Twenty-four hours after surgery, CLP mice were further randomized to receive saline, adipose tissue-derived (AD)-MSCs (105, nonpreconditioned), or AD-MSCs preconditioned with EPA for 6 h (105, EPA-preconditioned MSCs) intravenously. After 24 h, survival rate, sepsis severity score, lung mechanics and histology, protein level of selected biomarkers in lung tissue, cellularity in blood, distal organ damage, and MSC distribution (by technetium-99m tagging) were analyzed. Additionally, the effects of EPA on the secretion of resolvin-D1 (RvD1), prostaglandin E2 (PGE2), interleukin (IL)-10, and transforming growth factor (TGF)-β1 by MSCs were evaluated in vitro.ResultsNonpreconditioned and EPA-preconditioned AD-MSCs exhibited similar viability and differentiation capacity, accumulated mainly in the lungs and kidneys following systemic administration. Compared to nonpreconditioned AD-MSCs, EPA-preconditioned AD-MSCs further reduced static lung elastance, alveolar collapse, interstitial edema, alveolar septal inflammation, collagen fiber content, neutrophil cell count as well as protein levels of interleukin-1β and keratinocyte chemoattractant in lung tissue, and morphological abnormalities in the heart (cardiac myocyte architecture), liver (hepatocyte disarrangement and Kupffer cell hyperplasia), kidney (acute tubular necrosis), spleen (increased number of megakaryocytes and lymphocytes), and small bowel (villi architecture disorganization). EPA preconditioning of MSCs resulted in increased secretion of pro-resolution and anti-inflammatory mediators (RvD1, PGE2, IL-10, and TGF-β).ConclusionsCompared to nonpreconditioned cells, EPA-preconditioned AD-MSCs yielded further reductions in the lung and distal organ injury, resulting in greater improvement in sepsis severity score and higher survival rate in CLP-induced experimental sepsis. This may be a promising therapeutic approach to improve outcome in septic patients.

Acute pulmonary toxicity following inhalation exposure to aerosolized VX in anesthetized rats

ABSTRACTThis study evaluated acute toxicity and pulmonary injury in rats at 3, 6 and 24 h after an inhalation exposure to aerosolized O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX). Anesthetized male Sprague-Dawley rats (250–300 g) were incubated with a glass endotracheal tube and exposed to saline or VX (171, 343 and 514 mg×min/m3 or 0.2, 0.5 and 0.8 LCt50, respectively) for 10 min. VX was delivered by a small animal ventilator at a volume of 2.5 ml × 70 breaths/minute. All VX-exposed animals experienced a significant loss in percentage body weight at 3, 6, and 24 h post-exposure. In comparison to controls, animals exposed to 514 mg×min/m3 of VX had significant increases in bronchoalveolar lavage (BAL) protein concentrations at 6 and 24 h post-exposure. Blood acetylcholinesterase (AChE) activity was inhibited dose dependently at each of the times points for all VX-exposed groups. AChE activity in lung homogenates was significantly inhibited in all VX-exposed groups at each time point. All VX-exposed animals assessed at 20 min and 3, 6 and 24 h post-exposure showed increases in lung resistance, which was prominent at 20 min and 3 h post-exposure. Histopathologic evaluation of lung tissue of the 514 mg×min/m3 VX-exposed animals at 3, 6 and 24 h indicated morphological changes, including perivascular inflammation, alveolar exudate and histiocytosis, alveolar septal inflammation and edema, alveolar epithelial necrosis, and bronchiolar inflammatory infiltrates, in comparison to controls. These results suggest that aerosolization of the highly toxic, persistent chemical warfare nerve agent VX results in acute pulmonary toxicity and lung injury in rats.

Accuracy of high resolution CT in assessing idiopathic pulmonary fibrosis histology by objective morphometric index.

To determine the accuracy of HRCT in assessing histology by objective morphometric index, twenty-five biopsy specimen-proved UIP were correlated with high-resolution CT (HRCT) by morphometric analysis. The scans were evaluated for the presence and extent of normal parenchyma, ground-glass attenuation, linear opacities, consolidation, honeycombing, vessels and bronchiectasis, and overall extent of histology involvement for normal parenchyma, honeycombing, alveolar septal inflammation, fibrosis, vessels, and bronchiectasis/bronchiolectasis. The comparison between morphometric measurements showed a strong correlation between HRCT and histologic parameters for extension (%) of normal tissue (p = 5 x 10(-5)), honeycombing (p = 6 x 10(-5)), and vessels (p = 0.0047). HRCT consolidation strongly correlated with alveolar septal inflammation (p = 0.015), whereas HRCT linear opacities had the highest correlation with histology for bronchiectasis or bronchiolectasis (p = 0.03). These associations also demonstrated that there was considerable residual scatter about the linear relationships found. By contrast, neither the ground glass patterns nor the bronchioectatic patterns determined by CT were associated with any histologic observation (p < 0.1). There was a borderline negative relationship between vessels determined by CT and histologic fibrosis (p = 0.069), i.e., the percentage of vessel patterns determined by CT was found to be lower when fibrosis was prominent histologically. Our results showed that HRCT patterns, usually employed to provide information about activity (ground glass) and fibrosis (consolidation) in IPF, failed to correlate with histology. On the other hand, chronic cystic lesions had a good correlation with histology. This finding suggests that in patients without a diffuse honeycomb pattern on HRCT, a lung biopsy may provide additional information. The more important limitation of our study was the lack of correlation related to the proximity of the biopsy site to the HRCT location evaluated by morphometry.

Usual Interstitial Pneumonia

The authors estimate the relationship between the progression of honeycombing and disease activity of usual interstitial pneumonia (UIP) by open lung biopsy specimen and ground-glass opacity on thin-section computed tomography (CT). Open lung biopsy specimens and the initial and follow-up thin-section CT of 29 patients with proven UIP are reviewed. Follow-up thin-section CTs were performed from 2 to 61 months (mean, 15.3 months) after biopsy. The interval between the initial CT and open lung biopsy was from 2 to 30 days (mean, 10.0 days). Areas of ground-glass opacity and honeycombing were quantified respectively on each CT slice by using a 0%-100% scale with 10% increments. Each open lung biopsy specimen was scored semiquantitatively for alveolar desquamation, alveolar septal inflammation, inflammatory airway narrowing, obstructive pneumonitis, and lymphoid nodules. Patients were classified into either a mild or severe activity group according to the median value of the pathologic score and the median value of the area of ground-glass opacity. The authors compared the progression of honeycombing on follow-up thin-section CT between the groups. The progression of honeycombing in UIP was significantly faster in the severe activity group than in the mild group according to the pathologic score (p = 0.003) and the area of ground-glass opacity (p = 0.0024). In patients with UIP, more active inflammation of the pulmonary interstitium results in faster progression of honeycombing in long-term follow-up.

Bronchiolitis obliterans with organising pneumonia: outcome.

Bronchiolitis obliterans with organising pneumonia (BOOP) is a distinct clinical pathologic syndrome. Most patients experience a good response to therapy, and death from progressive BOOP is uncommon. This report describes the clinical features, etiologic factors, pathologic findings, and outcome of 10 patients with rapidly progressive BOOP that was characterised by severe respiratory failure. The major clinical manifestations were dyspnea, cough, fever, crackles on chest examination, and hypoxemia at rest. Underlying conditions or exposures included connective-tissue disease, exposure to birds, and chronic nitrofurantoin therapy. All patients had the characteristic histopathologic findings of BOOP. However, at autopsy in six patients, the predominant histologic pattern was that of alveolar septal inflammation and fibrotic honeycombing. Seven patients died and three patients survived but had persistent pulmonary dysfunction despite aggressive care. In two patients BOOP has progressed, with severe chronic respiratory decompensation. Thus, there is a subset of patients with BOOP who present with a fulminant course leading to death or chronic severe fibrosis and marked impairment of lung function. In addition, the histologic picture of BOOP may be a manifestation of early lung injury that can resolve or progress rapidly to alveolar septal inflammation, end-stage fibrosis, and honeycombing. (Am J Respir Crit Care Med 1994 ;149 :1670-5)

Influence of various factors on glucocorticoid receptors of bronchoalveolar lavage (BAL) cells from rabbits

It is supposed that the effects of glucocorticoid on target cells are mediated by glucocorticoid receptors. Recent investigations have demonstrated that changes in the composition and function of immune cells in bronchoalveolar lavage (BAL) cells of patients with immunological lung diseases are associated with the intensity of alveolar septal inflammation, or indicate steroid responsiveness. In order to clarify the physiologic changes of glucocorticoid receptor (GR) we measured the GR content of BAL cells obtained from rabbits with various conditions of the host (aging, immunological activation, malnutrition and pretreatment with prednisolone). The specific binding to GR was carried out by incubating BAL cells with 1, 2, 4, 10, 20, 40 nM 3H-prednisolone in the presence or absence of 1.0 x 10(-6) M unlabeled prednisolone. BAL cells from rabbits of various ages exhibited age-dependent reduction of GR content. There were striking differences of GR content in BAL cells from normal and BCG-vaccinated rabbits. The former yielded 3124 +/- 365 binding sites per cell, whereas activated BAL cells showed considerably higher values (6807 +/- 766). Chronological changes in GR content in BAL cells were also observed in normal rabbits pretreated with intravenous injection of prednisolone (2 mg/kg). The GR content was lowest at 3 hours after administration, reaching a peak at two days and then returned to control level. As for nutritional modulation, GR content tended to increase in the initial phase of fasting (days 4 to 8), and then decreased after day 12. In contrast, there were no significant changes in dissociation constants among BAL cells from animals in normal, immunologically activated and malnourished conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy.

Analysis of bronchoalveolar lavage cellular constituents has been recommended as a valuable method for the characterization of the inflammatory cellular population and for studying cellular interactions in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF). However, the clinical relevance of the enumeration of cells in bronchoalveolar lavage fluid (BALF) from patients with IPF remains controversial. We therefore examined the correlations between BALF cellular constituents and both the histopathologic abnormalities and the subsequent clinical response to corticosteroid therapy in 26 newly diagnosed, untreated patients with IPF. The BALF lymphocytosis was associated with moderate-to-severe alveolar septal inflammation (p less than 0.0005) and with a relative lack of histologic honeycombing (p less than 0.05). On the other hand, BALF neutrophil and eosinophil contents did not significantly correlate with any of eleven particular histopathologic abnormalities, and BALF neutrophil and lymphocyte contents did not correlate with the degree of clinical impairment (quantitated by a composite score based on dyspnea, radiographic abnormalities, and physiologic impairment) upon presentation. However, BALF eosinophil content correlated significantly with the severity of clinical impairment, higher eosinophil counts being associated with more severe initial clinical impairment (p less than 0.01). Neither pretreatment BALF neutrophil nor eosinophil content was related to the frequency or magnitude of subsequent clinical change in 20 patients evaluated before and after 1 yr of corticosteroid therapy. In contrast, pretreatment BALF lymphocytosis was associated with significant subsequent clinical improvement (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Diffuse interstitial pneumonitis: Clinicopathologic correlations in 20 patients treated with prednisone/azathioprine

Twenty patients with diffuse interstitial pulmonary disease diagnosed by open lung biopsy received combined prednisone/azathioprine therapy. Twelve patients demonstrated improvement with therapy. Each patient's clinical presentation, roentgehologic features and pathologic findings were correlated with their therapeutic response. Patients with an illness of one year's duration or less had a more favorable response to therapy than patients with a greater than two year duration of illness. Patients with associated extrathoracic abnormalities (anemia, glomerulitis, hepatopathy) exhibited a better therapeutic response than those with only pulmonary disease. The biopsy material from each patient was quantitatively graded on 20 morphologic variables. Statistical analysis using multiple linear regression revealed that a single variable, degree of interstitial fibrosis, was more than 90 per cent accurate in separating those responsive to therapy from those who failed to respond. Patients who respond to treatment had less interstitial fibrosis. Neither the amount of alveolar septal inflammation nor intra-alveolar cellular reaction was discriminatory in predicting response to therapy. A beneficial response to therapy was reflected in both improved lung volumes and gas exchange. Eight patients appeared to have a selective beneficial effect from azathioprine.