Lipid-laden Alveolar Macrophages Research Articles

Alveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death

Alveolar macrophages (AM) hold lung homeostasis intact. In addition to the defense against inhaled pathogens and deleterious inflammation, AM also maintain pulmonary surfactant homeostasis, a vital lung function that prevents pulmonary alveolar proteinosis. Signals transmitted between AM and pneumocytes of the pulmonary niche coordinate these specialized functions. However, the mechanisms that guide the metabolic homeostasis of AM remain largely elusive. We show that the NK cell-associated receptor, NKR-P1B, is expressed by AM and is essential for metabolic programming. Nkrp1b−/− mice are vulnerable to pneumococcal infection due to an age-dependent collapse in the number of AM and the formation of lipid-laden AM. The AM of Nkrp1b−/− mice show increased uptake but defective metabolism of surfactant lipids. We identify a physical relay between AM and alveolar type-II pneumocytes that is dependent on pneumocyte Clr-g expression. These findings implicate the NKR-P1B:Clr-g signaling axis in AM-pneumocyte communication as being important for maintaining metabolism in AM.

E-cigarette or vaping product use-associated lung injury: A review of clinico-radio-pathological characteristics.

Aggressive, albeit false marketing of electronic nicotine delivery systems (ENDS) or vaping devices as safer alternatives to cigarette smoking, combined with lack of regulations, has led to its mass adoption, especially among youth. A sudden increase in acute lung injuries was noted in 2019 which was linked to ENDS. It was termed by the Centers for Disease Control and Prevention (CDC) as electronic cigarette or vaping product use-associated lung injury (EVALI). Analysis of bronchoalveolar lavage fluid samples linked EVALI to vitamin E acetate (VEA), which is used as a diluting agent for marijuana oils. Patients with EVALI present with a combination of non-specific respiratory, gastrointestinal, and systemic symptoms. Laboratory results may show elevated inflammatory biomarkers. EVALI is a diagnosis of exclusion and must meet the following criteria: i) history of vaping within last 90 days, ii) abnormal chest imaging, iii) negative evaluation for infection, and iv) no other plausible diagnosis. A spectrum of computed tomography (CT) chest findings has been reported in EVALI, ranging from diffuse alveolar damage to organizing pneumonia, characterized by bilateral ground-glass opacities, consolidation, and septal thickening. A similar spectrum is seen on histopathology, characterized by lipid-laden alveolar macrophages, with varying degrees of infiltrative inflammatory cells and fibrin deposition. Early and accurate identification of the EVALI pattern can help optimize patient care. For example, in diffuse alveolar damage (DAD), a lower threshold for ventilation support and corticosteroid may improve outcomes. Here, we review the etiopathogenesis, clinical management, histopathology, and imaging features of EVALI.

Clinical outcomes and lipid-laden macrophages in Electronic cigarette/Vaping product use-Associated Lung Injury (EVALI) in a South Texas population

Objective: To describe the clinical features, proportion of lipid-laden alveolar macrophages in bronchoalveolar lavage (BAL), and short-term and 6-month to 12-month outcomes of patients with Electronic cigarette/Vaping product use-Associated Lung Injury (EVALI).Methods: Retrospective review of clinical characteristics, radiographs, and BAL samples for all patients with a history of vaping who presented with acute hypoxemic respiratory failure to the University Hospital in San Antonio, Texas from 9/2019 to 6/2020 was performed.Results: We report 16 cases (15 men; median age, 30 years [range 19-75]) of EVALI with a history of vaping Tetrahydrocannabinol (THC), nicotine, or both. The most common presenting symptoms were tachycardia, dyspnea, cough, and fever. All patients required supplemental oxygen, including two who required noninvasive positive pressure ventilation, and five who required mechanical ventilation. All 16 patients had bilateral ground-glass opacities (GGO) with peripheral sparing on chest computerizedtomography (CT). Cultures were negative, except for one patient who tested positive for rhinovirus. COVID-19 PCR was done in one individual which was negative. Cytology demonstrated lipid-laden macrophages on Oil-Red-O stain on fresh (i.e., without fixative) BAL in the majority of patients (N = 12) with a mean lipid-saturation percentage of 78% [range, 44%-100%] and the mean Colombo count of 194 [range, 101-359]. Fifteen patients were treated with systemic corticosteroids. The median length of hospital stay was 10 days. At discharge, three patients required supplemental oxygen. Eight of those who had follow-up imaging showed resolution of GGO. One patient had a relapse of symptoms and was again treated with systemic corticosteroids and mycophenolate, with resolution of symptoms. Fourteen patients who were evaluated after discharge denied vaping post-discharge (two patients were not able to be contacted and did not keep follow-up appointments).Conclusions: Successful diagnosis and management of EVALI requires a high clinical suspicion, thorough evaluation to rule out infectious etiologies, and aggressive treatment with systemic corticosteroids, along with sustained abstinence from vaping.

EVALI-ASSOCIATED LIPID LADEN MACROPHAGES: CASE SERIES IN SOUTH TEXAS

SESSION TITLE: Tobacco Cessation and Prevention Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: To describe the clinical features, proportion of lipid-laden alveolar macrophages in bronchoalveolar lavage (BAL), and outcomes of patients with Electronic cigarette/Vaping-Associated Lung Injury (EVALI). METHODS: Clinical characteristics, radiographs, and BAL samples were reviewed for all patients with a history of vaping who presented with acute hypoxemic respiratory failure to the University Hospital in San Antonio, Texas from 9/2019 to 5/2020. RESULTS: We report 10 cases (9 men; median age, 32 years [range, 22-44]), with a history of vaping Tetrahydrocannabinol (THC). The most common signs/symptoms were tachycardia (N=10), dyspnea (N=9), cough (N=6), productive cough (N=3), and fever (N=6) occurring at least 1-28 days (median, 7 days) prior to presentation. All patients required supplemental oxygen, 5 required high-flow nasal cannula, and 3 required mechanical ventilation. Bilateral ground-glass opacities (GGO) with peripheral sparing on computerized tomography (CT) chest were noted in all patients. Sputum and blood cultures were all negative, except for one who had rhinovirus on the respiratory viral panel. Due to high clinical suspicion of EVALI, bronchoscopy was performed and cytology demonstrated lipid-laden macrophages on the oil-red-O stain on BAL in all patients (N=10) with a mean lipid-saturation percentage of 79% [range, 44-100%] and the mean Colombo count of 194 [range, 101-359]. All but one patient was treated with systemic corticosteroids (5 before bronchoscopy, 4 following bronchoscopy). Medium time to steroid administration was 3 days with an outpatient taper. The median length of stay was 10 days [range, 4-25 days]. No patients required supplemental oxygen at discharge. All 7 of those who had follow-up imaging at 6-12 weeks showed resolution of GGO and all 10 patients reported symptom resolution and no further vaping after discharge. CONCLUSIONS: We present a case series describing the diagnosis and successful management of patients with EVALI based on maintaining a high clinical suspicion, appropriate diagnostic testing including labs, imaging, and bronchoscopy with BAL stains for lipid-laden macrophages, as well as routine studies to rule out infectious etiologies, followed by early and aggressive treatment with systemic corticosteroids. CLINICAL IMPLICATIONS: Currently, no particular test has been identified to confirm EVALI. Diagnosis is based on a high clinical suspicion in patients with vaping exposure, as well as obtaining classic imaging and laboratory tests to rule out other potential etiologies. Bronchoscopy and BAL with lipid stains in the appropriate clinical setting may assist clinicians in early diagnosis and in decisions regarding initiating aggressive corticosteroid therapy in these patients. Counseling about vaping cessation is also critical for these patients. DISCLOSURES: Unrestricted grant for CME research relationship with AstraZeneca Please note: $20001 - $100000 Added 05/31/2020 by Sandra Adams, source=Web Response, value=Grant/Research Support Unrestricted grant for CME research relationship with Boehringer Ingelheim Please note: $20001 - $100000 Added 05/31/2020 by Sandra Adams, source=Web Response, value=Grant/Research Support Unrestricted grant for CME research relationship with GlaxoSmithKline Please note: $20001 - $100000 Added 05/31/2020 by Sandra Adams, source=Web Response, value=Grant/Research Support Unrestricted grant for CME research relationship with Sunovion Please note: $20001 - $100000 Added 05/31/2020 by Sandra Adams, source=Web Response, value=Grant/Research Support Support for continuing medical education relationship with Mylan/Theravance Please note: $1001 - $5000 Added 05/31/2020 by Sandra Adams, source=Web Response, value=nebulizer/meds for teaching No relevant relationships by Moeezullah Beg, source=Web Response No relevant relationships by Mahnoor Mir, source=Web Response No relevant relationships by Jay Peters, source=Web Response

Fat Embolism and Severe Natural Disease: Challenges for Certification

Detectable intravascular fat has been reported in up to 90% of patients with long bone fractures. However, the more clinically significant fat embolism syndrome (FES) is less common. Despite its common occurrence, determining the significance of fat embolism as a cause of death remains controversial; however, helpful objective criteria through a tiered approach have recently been proposed. Patients with coexisting natural disease and fat embolism present an additional challenge for interpretation. We present an illustrative 59-year-old woman with severe comorbidities who died 11 days following a femoral neck fracture and discuss how the use of special techniques to demonstrate embolic fat and published guidelines for diagnosis were helpful in death certification. The case also provides a beautiful morphologic illustration of the accumulation of lipid laden alveolar macrophages as intravascular fat is absorbed into the tissues over time. Such macrophages can also be clinically detected by bronchoalveolar lavage, which can provide some objective support for a clinically suspected diagnosis of fat embolism.

Gastroesophageal Reflux

Gastroesophageal Reflux

Lipid-Laden Alveolar Macrophages and pH Monitoring in Gastroesophageal Reflux-Related Respiratory Symptoms.

Lipid-laden alveolar macrophages and pH monitoring have been used in the diagnosis of chronic aspiration in children with gastroesophageal reflux (GER). This study was conducted to prove a correlation between the detection of alimentary pulmonary fat phagocytosis and an increasing amount of proximal gastroesophageal reflux. It was assumed that proximal gastroesophageal reflux better correlates with aspiration than distal GER. Patients from 6 months to 16 years with unexplained recurrent wheezy bronchitis and bronchial hyperreactivity, or recurrent pneumonia with chronic cough underwent 24-hour double-channel pH monitoring and bronchoscopy with bronchoalveolar lavage (BAL). Aspiration of gastric content was determined by counting lipid laden alveolar macrophages from BAL specimens. There were no correlations between any pH-monitoring parameters and counts of lipid-laden macrophages in the whole study population, even when restricting analysis to those with abnormal reflux index expressing clinically significant GER. Quantifying lipid-laden alveolar macrophages from BAL in children with gastroesophageal-related respiratory disorders does not have an acceptable specificity to prove chronic aspiration as an underlying etiology. Therefore, research for other markers of pulmonary aspiration is needed.

特発性間質性肺炎の治療中に,左大腿骨頸部骨折を契機に急激な呼吸不全を呈した脂肪塞栓症候群の1例

A 78 year old Japanese woman was transferred to our hospital for the treatment of a fracture of the left femoral neck in April, 2010. She had been taking oral corticosteroid (prednisolone 5 mg/day) for the treatment of idiopathic interstitial pneumonia since 2003, and had been treated by home oxygen therapy since 2007. She fell in the restroom at home and hurt herself, and was transferred to our hospital for treatment of a left femoral neck fracture in April, 2010. Her respiratory status was stable just after the transfer; however, she was transferred to the intensive care unit and started to receive mechanical ventilation due to rapidly progressive respiratory failure on the fourth day after admission. Chest X-ray and computed tomography revealed rapid progression of bilateral ground-glass attenuations, and acute exacerbation of interstitial pneumonia was clinically suspected. However, the elevation of D-dimer over time and characteristic findings of petechial hemorrhagic lesions on her palpebral conjunctivae and neck with microscopic findings of phagocytized lipid in alveolar macrophages in her endobronchial secretion led to the diagnosis of fat embolism syndrome. She was successfully treated with high-dose corticosteroid and sivelestat sodium, and she was discharged on the 21st day after admission. Although a differential diagnosis of acute exacerbation of interstitial pneumonia and fat embolism syndrome was necessary and difficult in the present case, characteristic findings of petechial hemorrhagic lesions of skin, palpebral conjunctiva and lipid-laden alveolar macrophages in endotracheal aspirate were useful for the accurate and prompt diagnosis of fat embolism syndrome.

Usefulness and safety of double endoscopy in children with gastroesophageal reflux and respiratory symptoms

Management of children with gastroesophageal reflux disease (GORD) and difficult-to-treat (D-T-T) respiratory symptoms may include double fiberoptic, airway and oesophago-gastro-duodenoscopies (DE). A study was performed to evaluate the usefulness and safety of DE in children with severe GORD and D-T-T respiratory symptoms. A 3-year retrospective review of records of children who underwent DE under general anaesthesia was performed: the relevant clinical information obtained and the occurrence of complications in the 72h following the DE. Inflammatory changes of the airways were found at bronchoscopy in 40 out of the 60 children: bronchoalveolar lavage (BAL) demonstrated positive lipid-laden alveolar macrophages (LLAM), neutrophilic inflammation or both, respectively in 9, 12 and 16 patients. BAL bacterial cultures were positive in 2 patients with elevated airway neutrophilia. Structural airway abnormalities, explaining not GOR-related D-T-T respiratory symptoms were identified in 11 patients. Oesophagoscopic findings supporting GORD were detected in 32/60 children and confirmed by consistent histological changes in oesophageal mucosal biopsies (OEB) in 27. The frequency of complications, all minor, was low during the procedure and in the following 72h. They included mild desaturation, stridor or bronchospasm, vomiting, dysphagia and hyperthermia requiring antibiotic treatment in 1 patient. No "new onset" complication was observed after 48h following DE. The time-dependent hazard of complications was significantly higher for patients with a history of onset of respiratory symptoms early in life (</=2 years of age) (p=0.038). DE can be useful in the clinical evaluation of children with D-T-T respiratory symptoms and GORD and is associated with low frequency of mild complications when performed by appropriately trained and experienced personnel.

Hydrocarbon pneumonitis following liquid paraffin aspiration during a fire-eating performance: a case report

IntroductionHydrocarbon pneumonitis is an acute, intense pneumonitis resulting from aspiration of volatile hydrocarbon compounds with low viscosity and surface tension, most of which are members of the paraffin, naphthene and aromatic classes.Case presentationSix hours after participating in a party for teenagers, a 16-year-old boy developed dyspnea, cough, a fever (39°C) and chest pain. A chest radiograph showed infiltration in the right middle lobe. The patient reported alcohol abuse during the party and an episode of vomiting a few hours thereafter. He also reported practicing a fire-eating performance at the party using liquid paraffin, but was unaware of inhaling any of it. The radiographic infiltration was diagnosed as an aspiration pneumonia and he was treated at the local health center with antibiotics. Five days later, because of clinical deterioration, he was referred to a pulmonary clinic. A chest computed tomography scan was performed which showed consolidation with an air bronchogram in the right middle lobe and areas of atelectasis and ground glass opacities in the middle and lower right lobes. Spirometry revealed severe restriction of lung function. A bronchoscopy revealed inflamed, hyperemic mucosa. Bronchoalveolar lavage fluid revealed lipid-laden alveolar macrophages, which were detected by lipid staining, and neutrophilia. The patient was finally diagnosed with hydrocarbon pneumonitis and he was treated with systemic steroids and antibiotics. After 6 days of treatment there was complete clinical and significant radiologic regression.ConclusionHydrocarbon pneumonitis should be included in the differential diagnosis of pneumonias. Recent exposure to volatile hydrocarbons provides a basis for clinical diagnosis, as symptoms and radiologic findings are not specific.

Cutoff value of lipid‐laden alveolar macrophages for diagnosing aspiration in infants and children

Chronic passage of gastric and/or alimentary material into the airways is a frequent and difficult-to-diagnose condition. Because alveolar macrophages phagocytose aspirated material, it has been suggested that their identification is a useful diagnostic method. To know the usefulness of the lipid-laden alveolar macrophages (LLAM) index as a diagnostic tool for aspiration, children from 1 month to 16 years of age were included in three groups: G-I, children with pulmonary pathology and suspicion of aspiration by clinic or image evaluation; G-II, with pulmonary pathology without suspicion of aspiration; and G-III, without respiratory symptoms nor suspicion of aspiration. Bronchoalveolar lavage was obtained through bronchoscopy in G-I and G-II, and through endotracheal tube in G-III, and the LLAM index (0-400) was determined. A total of 112 patients (41, 30, and 41 in G-I to III, respectively) were studied. LLAM index (mean +/- SEM) was highest in G-I (233.2 +/- 5.5), as compared with G-II (187.8 +/- 11.6, P < 0.05), and G-III (108.5 +/- 13.5, P < 0.001). However, notable overlap of LLAM values was observed between G-I and G-II, and between G-II and G-III. When patients from G-I and G-III were jointly analyzed, the area under the ROC curve for diagnosing aspiration was 0.92, with a best cutoff value of >165 (98.6% sensitivity, 78.0% specificity, 87.8% overall accuracy). LLAM index, with a cutoff value of >165 is a useful diagnostic test for aspiration when there is suspicion of this condition. However, due to its low specificity, it does not discriminate other causes of chronic lung disease.

Lipid-laden alveolar macrophages in induced sputum in patients with gastroesophageal reflux disease

Lipid-laden alveolar macrophages in induced sputum in patients with gastroesophageal reflux disease

Effects of multiple pulmonary aspirations of enteral solutions on lung tissue damage

The aim of this study was to compare the pulmonary histopathologic effects of enteral solutions with various lipid content, after multiple aspirations in rats. Thirty Wistar albino rats were randomly assigned to one of three groups (n = 10). Saline solution (0.9%) (group C, control), Impact (lipid content, 28 g/l; group I), Pulmocare (lipid content, 93.3g/l; group P) were injected into the lung through the trachea, in a volume of 0.8 ml/kg. The aspiration procedure was performed three times in total, in every 2 days. After seven days from the first aspiration, rats were killed, and lungs were examined for histopathologic examination. Alveolar histiocytes were statistically higher in left lungs of the group I than the left ones of the control group (P < 0.05). Lipid-laden alveolar macrophages were significantly higher in left lungs of groups I and, P than left lungs of the control group (P<0.05). Lung tissue damage occurring after multiple pulmonary aspirations of Impact and Pulmocare, is histopathologically similar to each other, and is in the form of lipoid pneumonia. In cases of multiple pulmonary aspirations, volume of the aspirate and chronicity of the aspiration look like major impact factors rather than the amount of the lipid.

Charcoal is a sensitive, specific, and stable marker for the diagnosis of aspiration in hamsters.

The diagnosis of recurrent aspiration in young children is a perpetual challenge because there is no specific gold standard test to be used. The finding of lipid-laden alveolar macrophages in bronchoalveolar lavage (BAL) is a sensitive but nonspecific marker for the diagnosis of aspiration. We conducted a short-term study comparing tracheal instillation of saline, milk, or a milk-charcoal mixture in hamsters. BAL cytology, lipid-laden alveolar macrophage index, charcoal alveolar macrophage index, and lung histology were monitored for 10 d. A long-term study was performed, and hamsters were monitored for 92 d after milk-charcoal tracheal instillation. Baseline animals (n = 4) had no tracheal instillation. Saline- and milk-instilled animals had BAL performed after 1 (n = 4), 3 (n = 4), and 10 (n = 4) d. Milk-charcoal-instilled animals had BAL performed after 1 (n = 4), 3 (n = 4), 10 (n = 4), 30 (n = 2), 58 (n = 2), and 92 (n = 2) d after tracheal instillation. Total cell counts and percent neutrophils in BAL fluid increased significantly and similarly after milk and milk-charcoal instillation on d 1 compared with baseline and saline-instilled animals. Lipid-laden alveolar macrophage index increased significantly only on d 3 after milk and milk-charcoal instillation compared with all days in the saline-instillation group. Charcoal alveolar macrophage index increased significantly after milk-charcoal instillation (d 1-58) from baseline or all days in the saline-instillation group. We conclude that charcoal particles instilled in tracheas of hamsters can be easily identified in BAL fluid and in lung parenchyma for as long as 3 mo after a single instillation and could potentially be used as a sensitive, specific, and stable marker for the diagnosis of aspiration, although the issue of its applicability to humans is still unsolved.

Bronchoalveolar lavage and esophageal pH monitoring data in children with ?difficult to treat? respiratory symptoms

Gastroesophageal reflux (GER) may be associated with chronic or recurrent asthma-like symptoms secondary to bronchoconstrictor reflexes and/or inhalation of gastric content. The presence of lipid-laden alveolar macrophages has been proposed as an index to establish the degree of gastric aspiration. We evaluated 20 children with "difficult to treat" respiratory symptoms and a clinical history suggestive of GER. All children underwent 24-hr esophageal pH monitoring (pHm) and fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). The amount of lipid per single macrophage was determined by a semiquantitative method, using fluorescence microscopy to detect Nile-Red-stained BAL cells and calculating a lipid-laden macrophage index (LLMI). Eleven children had positive pHm recordings, suggesting the presence of GER (pH-positive patients), and 9 had negative pHm records (pH-negative patients). The pH-positive patients had higher percentages of neutrophils and higher LLMI than the pH-negative children (P < 0.05). There were no correlations between the pHm records and either % BAL neutrophils or LLMI in pH-positive or pH-negative patients (P > 0.05; each correlation). In contrast, a single correlation was found between % BAL neuytrophils and LLMI, both in the pH-positive and in the pH-negative patients (r = 0.72, P = 0.02 and r = 0.71, P = 0.04, respectively). These data demonstrate that a significant proportion of pH-positive patients with respiratory symptoms have BAL abnormalities that suggest airway inflammation and gastric content aspiration. However, the intensity of GER as indicated by pH monitoring does not correspond with BAL data in all patients.

Lipoid Pneumonia in Children:: Clinical and Imagenological Manifestations

Background Oil-aspiration pneumonia is still a health problem in countries where infants are forced to receive vegetable or animal oil due to traditional habits. The aim of this paper is to present clinical and imagenological characteristics of lipoid pneumonia (LP) in children and a review of the literature. Distinguishing features of and differences between other series are presented. Methods Series of cases. We retrospectively analyzed all records of children with lipoid pneumonia between 1991 and 1996. Results We found 16 patients aged 1–19 months old with positive oil ingestion in 75% and history of recurrent or persistent pneumonia in 81.2%. In almost 70% of patients, there were underlying conditions known as risk factors of aspiration. Plain films and computed tomography (CT) showed that the right lung was always involved. Fat density was found in only two cases. Bronchoscopy with bronchial lavage was performed in 15 patients, with lipophages positive in each patient. Conclusions Lipoid pneumonia must be ruled out in the differential diagnosis in infants with persistent or recurrent pneumonia with or without fever, especially in patients with aspiration risk factors. Bronchoscopy with bronchial lavage and positive lipid-laden alveolar macrophages proved a useful method for diagnosis of this condition. More studies are needed to ascertain the clinical and imagenological evolution of this condition.

Intratracheally applied rSP-C surfactant exhibits no anaphylactic shock reactions in a guinea pig model of acute lung hypersensitivity

The effect of the intratracheal administration of the recombinant SP-C surfactant apoprotein (rSP-C) with phospholipids (PL) in comparison to an ovalbumin induced anaphylactic shock reaction was studied in guinea pigs lungs. Narcotized guinea pigs were challenged by intratracheal administration on test day 24/25 once with a suspension of rSP-C/PL (reconstituted suspension). These animals were priorily sensitized on test day 1, 3 and 5 intraperitoneally with rSP-C/PL suspension or with Ovalbumin (OV) respectively. The following groups were used to assess the anaphylactic lung shock symptoms: group 1: positive control, 1 mg/kg OV protein, 2 ml/kg application volume, (Appl. vol.), N: 5 animals; group 2: 1 mg rSP-C/50 mg PL/0.5 ml/kg Appl. vol., N: 10; group 3: 2 mg rSP-C/100 mg PL/1.0 ml/kg Appl. vol., N: 10; group 4: 4 mg rSP-C/200 mg PL/2.0 ml/kg Appl. vol., N: 10. Clinical signs, mortality, lung weights and histopathological changes were evaluated. Additionally the lungs were investigated immunohistologically with polyclonal antibodies against rSP-C to determine the pulmonary distribution of the intratracheal applied rSP-C. In the OV-treated positive control group, all animals died within 4 minutes after intratracheal challenge, while only 1 animal of group 4 died probably due to an narcosis related respiratory arrest. In the rSP-C/PL treated groups, the lung weights showed a dose-related increase, but nevertheless all these rSP-C-treated groups showed a significant lower lung weight in comparison to the OV treated positive control group. The histopathology assessment of the lungs in the OV-treated animals revealed a severe generalised bronchoconstriction and a hyperemia in connection with a slight interstitial edema in all five animals. The rSP-C/PL-treated animals, which were sacrificed after 3 days, showed no bronchoconstriction but a slight increase in the severity of bronchus-associated infiltration with eosinophilic granulocytes and in the formation of peripheral emphysema, but with no dose-dependency. A slight dose-dependent increase in the deposition of peribronchiolar eosinophilic foreign material was evident. In contrast to this, the number of lipid-laden alveolar macrophages seemed to decrease with increasing doses of rSP-C/PL. The immunohistological investigation with a polyclonal antibody against rSP-C showed an intraalveolar distribution of the intratracheally applied rSP-C which is mainly located in the peribronchiolar alveolar parenchyma. A rSP-C-positive staining was visible within the cytoplasm of alveolar histiocytes, type II pneumocytes and also as an extracellularly rim along the alveolar walls. The polyclonal antibody showed no cross reaction with natural occuring SP-C-protein of the guinea pigs. We conclude that the intratracheal application of the rSP-C surfactant containing phospholipids (PL) exhibits no significant risk of an anaphylactic shock reaction in this guinea pig lung hypersensitivity model. The immunohistological investigation with polyclonal antibodies against rSP-C demonstrated clearly the distribution of intratracheal applied material in this toxicological animal model.

Lipid-laden alveolar macrophages (LLAM): a useful marker of silent aspiration in children.

At present there is no test available which identifies children suffering from silent aspiration due to gastroesophageal reflux (GER). The purpose of this study was to determine whether lipid-laden alveolar macrophage (LLAM) scoring is a useful method to arrive at the diagnosis. We evaluated bronchoalveolar lavage fluid (BALF) from 68 children aged 6 months to 14 years (median 3.75 years) for the presence of lipid-laden alveolar macrophages. We compared children with chronic chest disease (CCD) and GER to healthy surgical controls without known lung disease, and to children with recurrent pneumonia without GER. By grading the amount of intracellular Sudan Red-positive material, we determined a semiquantitative lipid-laden macrophage (LLAM) score for each patient. Patients with chronic chest disease suspected to be caused by silent aspiration secondary to GER had a significantly higher LLAM score (median, 117; range, 10-956) than children with recurrent pneumonia due to other reasons (median, 29; range, 5-127; P < 0.01) and healthy controls (median, 37; range, 5-188; P < 0.01). We believe that simply observing lipid-laden macrophages is nonspecific, but quantitation of these cells is a useful method for diagnosing silent aspiration in children, especially when the score exceeds 200.

Antireflux surgery in children suffering from reflux-associated respiratory diseases.

The aim of our study was to evaluate the success, complications, and morbidity following a modified Thal fundoplication in children with reflux-associated respiratory disease (RARD). We used a procedure consisting of retroesophageal hiatal plasty, wrapping the gastric fundus around the gastroesophageal junction 180 degrees, and fixation of the lesser curvature at the abdominal wall. Follow-up by questionnaire of 128 (77 male, 51 females) out of 196 antireflux procedures between 1992 and 1995 was achieved. Surgical therapy was considered justified whenever there was gastroesophageal reflux resulting in severe recurrent respiratory symptoms. Eleven percent of the children suffered from bronchiectasis. The diagnosis of RARD was based on a high index of suspicion, barium swallow with fluoroscopy, 24-hr two-level pH-monitoring, bronchoscopy, bronchoalveolar lavage and detection of lipid-laden alveolar macrophages, esophago-gastroscopy, and esophageal biopsy. Patients with bronchopulmonary diseases such as allergy, immunodeficiency, cystic fibrosis, primary ciliary dyskinesia, and malformation of the bronchial tree or vessels had been excluded. "Evident improvement" as a result of surgery was reported in 88%, "no change" in 10%, and a "change for the worse" in 2% of patients. Persistent mild difficulties in swallowing were observed in 11%. Paraesophageal hernia, gas-bloat syndrome, and dumping syndrome were not observed. Two children needed a second operation because of relapse. The use of emergency steroidal medication for acute respiratory distress decreased impressively (219 single doses/year before surgery vs. 30 single doses/year after surgery). The need for more than 4 times/year of antibiotic therapy before surgery was reduced from 52. 3% before to 14% after surgery. Most (90.6%) of the parents stated they would agree to have surgery done again if medically indicated. In conclusion, Thal fundoplication is sufficient, safe, and effective in the management of RARD. Complications of the procedure were minor and of little consequence to the patient.

Radiographic bilateral cavitary lesions in lipoid pneumonia

We report a case of lipoid pneumonia with pulmonary bilateral cavitated lesions. The diagnosis was based on the finding of abundant lipid-laden alveolar macrophages in bronchoalveolar lavage and the presence of histologic changes indicative of lipoid pneumonia in transbronchial lung biopsy.