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Concept: Bronchoalveolar lavage

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Asthma is associated with increased levels of eosinophils in tissues, body fluids, and bone marrow. Elevated levels of eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) have been noted in asthma patients. Higher levels of EDN and ECP are also associated with exacerbated asthmatic conditions. Thus, EDN, along with ECP, may aid the diagnosis and monitoring of asthma. Several groups have suggested that EDN is more useful than ECP in evaluating disease severity. This may partially be because of the recoverability of EDN (not sticky, 100% recovery rate), as ECP is a sticky and more highly charged protein. In terms of clinical utility, EDN level is a more accurate biomarker than ECP when analyzing the underlying pathophysiology of asthma. As a monitoring tool, EDN has shown good results in children with asthma as well as other allergic diseases. In children too young to fully participate in lung function tests, EDN levels may be useful as an alter native measurement of eosinophilic inflammation. EDN can also be used in adult patients and in multiple specimen types (e.g., serum, sputum, bronchoalveolar lavage fluid, and nasal lavage fluid). These results are repeatable and reproducible. In conclusion, EDN may be a novel biomarker for the diagnosis, treatment, and monitoring of asthma/allergic disease.

Concepts: Immune system, Pulmonology, Asthma, Allergy, Bronchoalveolar lavage, Spirometry, Peak flow meter, Eosinophil granulocyte

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The cystic fibrosis (CF) lung microbiome has been studied in children and adults; however, little is known about its relationship to early disease progression. To better understand the relationship between the lung microbiome and early respiratory disease, we characterized the lower airways microbiome using bronchoalveolar lavage (BAL) samples obtained from clinically stable CF infants and preschoolers who underwent bronchoscopy and chest computed tomography (CT). Cross-sectional samples suggested a progression of the lower airways microbiome with age, beginning with relatively sterile airways in infancy. By age two, bacterial sequences typically associated with the oral cavity dominated lower airways samples in many CF subjects. The presence of an oral-like lower airways microbiome correlated with a significant increase in bacterial density and inflammation. These early changes occurred in many patients, despite the use of antibiotic prophylaxis in our cohort during the first two years of life. The majority of CF subjects older than four harbored a pathogen dominated airway microbiome, which was associated with a further increase in inflammation and the onset of structural lung disease, despite a negligible increase in bacterial density compared to younger patients with an oral-like airway microbiome. Our findings suggest that changes within the CF lower airways microbiome occur during the first years of life and that distinct microbial signatures are associated with the progression of early CF lung disease.

Concepts: Bacteria, Diseases and disorders, Respiratory disease, Pulmonology, Pneumonia, Cystic fibrosis, Bronchoalveolar lavage, Obstructive lung disease

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Bronchiolitis obliterans syndrome (BOS), a condition of irreversible small airway fibrosis, is the principal factor limiting long-term survival after lung transplantation. Bronchoscopy and bronchoalveolar lavage (BAL), techniques central to lung transplant clinical practice, provide a unique opportunity to interrogate the lung allograft during BOS development and identify potential disease mechanisms or biomarkers. Over the past 20 years, numerous studies have evaluated the BAL cellular composition, cytokine profiles and protein constituents in lung transplant recipients with BOS. To date, however, no summative evaluation of this literature has been reported. We developed and applied objective criteria to qualitatively rank the strength of associations between BAL parameters and BOS in order to provide a comprehensive and systematic assessment of the literature. Our analysis indicates that several BAL parameters, including neutrophil count, interleukin-8, alpha defensins and MMP-9, demonstrate highly replicable associations with BOS. Additionally, we suggest that considerable opportunity exists to increase the knowledge gained from BAL analyses in BOS through increased sample sizes, covariant adjustment and standardization of the BAL technique. Further efforts to leverage analysis of BAL constituents in BOS may offer great potential to provide additional in-depth and mechanistic insights into the pathogenesis of this complex disease.

Concepts: Scientific method, Pulmonology, Evaluation, Cystic fibrosis, Assessment, Organ transplant, Bronchoalveolar lavage, Bronchiolitis obliterans

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A two-year-old Jack Russell terrier was presented for evaluation of chronic cough and exercise intolerance. Previous treatment with antibiotics and glucocorticoids had only partially ameliorated the clinical signs. During investigation, hypoxaemia, peripheral eosinophilia and an eosinophilic bronchoalveolar lavage fluid were noted. Thoracic radiographs revealed two ovoid clearly delineated soft-tissue opacities, one in the caudal segment of the left cranial lung lobe (diameter 26 mm) and the other in the right cranial lung lobe (diameter 20 mm). These findings were verified by computed tomography, which identified an additional smaller lesion (diameter 16 mm) dorsally in the right caudal lobe. Ultrasound-guided fine-needle aspiration samples confirmed the diagnosis of eosinophilic pulmonary granulomatosis and treatment with prednisolone and azathioprine was initiated. Within 1 month, granulomas were no longer detectable radiographically. All medication was discontinued after 7 months and currently, after 2·5 years, the dog remains free of clinical signs. To the authors' knowledge this is the first case report to describe prolonged remission from idiopathic canine eosinophilic pulmonary granulomatosis.

Concepts: Pulmonology, Asthma, Lung, Pneumonia, Left-wing politics, Tuberculosis, Bronchoalveolar lavage, Jack Russell Terrier

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Introduction. Besides hypogammaglobulinemia and recurrent infections, abnormalities of T-cells might contribute to lung damage in common variable immunodeficiency disorders (CVID). Materials and methods. In 16 adult patients, the majority of whom had pulmonary abnormalities, we studied T-cell subsets and markers of inflammation in bronchoalveolar lavage fluid (BALF) and blood and their relations with pulmonary function and high resolution computed tomography (HRCT). Results. We demonstrated that some of the lymphocyte abnormalities previously demonstrated in peripheral blood from CVID patients, such as low CD4/CD8 T-cell ratio, were also present in BALF. Moreover, low BALF CD4/CD8 ratio (≤ 1), found in seven patients, was significantly associated with higher blood CD8(+) cell count and to lower values of the lung function variables; forced expiratory volume (FVC), total lung capacity (TLC), vital capacity (VC) and residual volume (RV) in % of predicted. The expression of the inflammatory markers HLA-DR and CCR5 on T-cells was significantly higher, and the expression of CCR7 significantly lower, in BALF compared to blood, possibly reflecting an inflammatory/cytotoxic T-cell phenotype within pulmonary tissue in CVID. Furthermore, patients with bronchiectasis had higher concentrations of the pro-inflammatory cytokine TNFα in plasma, compared to those without. Conclusion. Our findings suggest that inflammation and T-cell activation may be involved in the immunopathogenesis of pulmonary complications in CVID.

Concepts: Immune system, Pulmonology, Asthma, Lung, Respiratory physiology, Bronchoalveolar lavage, Lung volumes, Spirometer

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Pneumocystis pneumonia (PCP) is caused by the yeastlike fungus Pneumocystis. Despite the widespread availability of specific anti-Pneumocystis prophylaxis and of combination antiretroviral therapy (ART), PCP remains a common AIDS-defining presentation. PCP is increasingly recognized among persons living in Africa. Pneumocystis cannot be cultured and bronchoalveolar lavage is the gold standard diagnostic test to diagnose PCP. Use of adjunctive biomarkers for diagnosis requires further evaluation. Trimethoprim-sulfamethoxazole remains the preferred first-line treatment regimen. In the era of ART, mortality from PCP is approximately 10% to 12%. The optimal time to start ART in a patient with PCP remains uncertain.

Concepts: Antiretroviral drug, HIV, AIDS, Africa, Diagnosis, Bronchoalveolar lavage, Pneumocystis pneumonia, Co-trimoxazole

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Silver, zinc oxide, and titanium dioxide nanoparticles are used as sterilisation materials to enhance the performance of disinfectants. We investigated the respiratory tract immune toxicity (“immunotoxicity”) of these nanoparticles in vivo and in vitro, and we explored the relationships between particle size, particle shape, chemical composition, chemical stability and the toxicological effects of these typical nanoparticles in rats. In vivo, the rats were exposed to nanoparticles by intratracheal instillation. Exposure to nanoparticles caused an increase in oxidative injury to the lungs and disorders in regulating the cytokine network, which were detected in the bronchoalveolar lavage fluid, suggesting that oxidative stress might be important for inducing the respiratory immunotoxicity of nanoparticles. In vitro, the phagocytic function of alveolar macrophages (AMs) was dose-dependently reduced by nanoparticles, and ZnO nanoparticles induced greater cytotoxicity than the silver and titanium-dioxide nanoparticles, which were coincident with the results of multiple measurements, such as a cell viability assay by WST-8 and LDH measurements. Comparative analyses demonstrated that particle composition and chemical stability most likely had a primary role in the biological effects of different nanoparticles.

Concepts: Ultraviolet, Pulmonology, Nitrogen, Aluminium, Zinc, Bronchoalveolar lavage, Titanium dioxide, Zinc oxide

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PURPOSE OF REVIEW: The aim is to discuss the clinical, microbiologic, and radiological criteria used in the diagnosis of ventilator-associated pneumonia (VAP), distinguish between ventilator-associated tracheobronchitis (VAT) and VAP, and reconcile the proposed Centers for Disease Control surveillance criteria with clinical practice. RECENT FINDINGS: Numerous ventilator-associated complications (VACs), including VAP and VAT, may occur in critically ill, intubated patients. A variety of definitions for identifying VAP have been proposed, but there is no diagnostic gold standard. The proposed surveillance definition will identify infectious and noninfectious VAC, including VAP and VAT, but this definition may be inadequate for clinical practice. SUMMARY: The clinical characteristics of VAP and VAT are similar and include fever, leukocytosis, and purulent sputum. An infiltrate on chest radiograph is consistent with VAP but lacks diagnostic precision, so it is not a criterion in the proposed surveillance definition and should be interpreted cautiously by clinicians. Microbiologically, quantitative and semiquantitative endotracheal aspirate cultures may be employed to diagnose VAP and VAT. Positive bronchoalveolar lavage and protected specimen brush cultures are useful only for the diagnosis of VAP. Experts should collaborate to develop consensus definitions for VAP and VAT that can be applied in practice.

Concepts: Pneumonia, Diagnosis, Bronchoalveolar lavage, Ventilator-associated pneumonia

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Objective-To evaluate protein expression in bronchoalveolar lavage fluid (BALF) obtained from West Highland White Terriers with idiopathic pulmonary fibrosis (IPF), dogs with chronic bronchitis, and healthy control dogs to identify potential biomarkers for IPF. Samples-BALF samples obtained from 6 West Highland White Terriers with histologically confirmed IPF, 5 dogs with chronic bronchitis, and 4 healthy Beagles. Procedures-Equal amounts of proteins in concentrated BALF samples were separated via 2-D differential gel electrophoresis. Proteins that were differentially expressed relative to results for healthy control dogs were identified with mass spectrometry and further verified via western blotting. Results-Expression of 6 proteins was upregulated and that of 1 protein was downregulated in dogs with IPF or chronic bronchitis, compared with results for healthy dogs. Expression of proteins β-actin, complement C3, α-1-antitrypsin, apolipoprotein A-1, haptoglobin, and transketolase was upregulated, whereas expression of lysozyme C was downregulated. Conclusions and Clinical Relevance-Proteomics can be used to search for biomarkers and to reveal disease-specific mechanisms. The quantitative comparison of proteomes for BALF obtained from dogs with IPF and chronic bronchitis and healthy dogs revealed similar changes for the dogs with IPF and chronic bronchitis, which suggested a common response to disease processes in otherwise different lung diseases. Specific biomarkers for IPF were not identified.

Concepts: Protein, Molecular biology, Pulmonology, Gel electrophoresis, Bronchoalveolar lavage, Idiopathic pulmonary fibrosis, Respiratory diseases, West Highland White Terrier

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The extracellular matrix (ECM) is a key regulator of tissue morphogenesis and repair. However, its composition and architecture are not well characterized. Here, we monitor remodeling of the extracellular niche in tissue repair in the bleomycin-induced lung injury mouse model. Mass spectrometry quantified 8,366 proteins from total tissue and bronchoalveolar lavage fluid (BALF) over the course of 8 weeks, surveying tissue composition from the onset of inflammation and fibrosis to its full recovery. Combined analysis of proteome, secretome, and transcriptome highlighted post-transcriptional events during tissue fibrogenesis and defined the composition of airway epithelial lining fluid. To comprehensively characterize the ECM, we developed a quantitative detergent solubility profiling (QDSP) method, which identified Emilin-2 and collagen-XXVIII as novel constituents of the provisional repair matrix. QDSP revealed which secreted proteins interact with the ECM, and showed drastically altered association of morphogens to the insoluble matrix upon injury. Thus, our proteomic systems biology study assigns proteins to tissue compartments and uncovers their dynamic regulation upon lung injury and repair, potentially contributing to the development of anti-fibrotic strategies.

Concepts: Pulmonology, Extracellular matrix, Fibrosis, Epithelium, Bronchoalveolar lavage, Proteomics, Proteome, Lavage