Biopsies And Bronchoalveolar Lavage Research Articles

Diagnostic yield and complications of flexible bronchoscopy performed at Charlotte Maxeke Johannesburg academic hospital: A 5 year restrospective study

Objectives: There is a high incidence of lung diseases but very little data in South Africa relating to bronchoscopy practice. The objectives of the study are to determine the diagnostic yield, indications, and complications as well as determine the effectiveness of biopsy and bronchoalveolar lavage (BAL) in making diagnoses of infectious and non-infectious diseases. Materials and Methods: Six hundred and ninety-two patients were identified and 647 cases were analyzed due to 45 cases with inadequate data for analyses. A single-center retrospective cross-sectional review of patients who underwent bronchoscopy between January 2015 and December 2019 was conducted at the Charlotte Maxeke Johannesburg Academic Hospital. Results: The epidemiology of the subjects showed a significant male predominance (64.14%), with a mean age of 55.9 years of age. The most common indication was suspected malignancy, followed by non-resolving pneumonia, 63.99%, and 14.53%, respectively. A total of 120 (18.55%) patients were diagnosed with a malignancy on biopsy and 83 (12.83%) on BAL. Of all bronchoscopies performed, 85.94% had no complications during or after bronchoscopy, whereas 10.97% were complicated with bleeding. Conclusion: This audit revealed that flexible bronchoscopy is safe and effective and associated with minimal risk. This study revealed the use of bronchoscopy in diagnosing lung malignancies/carcinomas and highlights the necessity of the availability of bronchoscopy.

Metformin for chemoprevention of lung cancer in high-risk overweight or obese individuals.

TPS10636 Background: Lung cancer is the most common cause of cancer-related deaths in the United States, with tobacco smoking being the most important risk factor. However, ~60% of individuals at a high risk for lung cancer or with early-stage lung cancer are either overweight or obese. Preliminary studies suggest that the diabetes drug metformin improves survival in high BMI lung cancer patients and inhibits lung cancer progression in preclinical models, likely through its effects on the obesity-triggered changes to the immune microenvironment of the lung, particularly, the regulatory T cells (Tregs) in the airway. Given the known dysregulation of Tregs in obesity and the importance of Tregs in lung carcinogenesis, we hypothesize that metformin therapy will reprogram the immune defense of obesity in directions that are consistent with the control of nascent lung tumor development. While more generalized lung cancer prevention approaches have to date shown limited effectiveness, the targeting of a specific subset of individuals at high risk for lung cancer provides a precision prevention approach, which is likely to be more effective. Methods: This is an open-label, randomized, wait-list control trial, where 50 non-diabetic obese/overweight former smokers with over 20 pack year smoking history and PLCOm2012 Lung Cancer Risk Prediction score above 1.34% will be enrolled. They will be equally randomized to either oral metformin or no treatment for 26 weeks followed by partial crossover, whereby no-treatment subjects will receive metformin for 26 weeks. The open-label, wait-list control design allows inclusion of a control group to assess stability of the primary biomarker in an untreated population while retaining the statistical power of 40 metformin-treated subjects (assuming 20% subject attrition) and will aid accrual since all trial participants will be treated. Treatment regimen is one daily dose of metformin at 500 mg for 1 week followed by 1000 mg for the second week and 2000 mg thereafter for a total of 24 weeks. Sampling for endpoint assessment include bronchoscopy with biopsy and bronchoalveolar lavage (BAL) and blood collection before and after completion of metformin treatment. The primary endpoint is to evaluate the effect of metformin treatment on the expression of PD-1, an immune checkpoint factor, on BAL Tregs. The secondary endpoints include stability of BAL Treg PD-1 expression over time and the impact of metformin on circulating immune cells. Trial sites include Roswell Park Comprehensive Cancer Center, the Rocky Mountain Regional Veterans Affairs Medical Center, and University of British Columbia, Vancouver. Since the trial opened to accrual in March 2022, 77 patients have been pre-screened and 19 were consented. Among them, 10 participants have been enrolled and randomized, 5 in each arm. We expect to complete accrual by April 2024. Clinical trial information: NCT04931017 .

An Unusual Presentation of Pulmonary Mucormycosis as a “Mass-like” Consolidation in an Infant with Chronic Granulomatous: A Case Report Study

Introduction: Chronic granulomatous disease (CGD) is a primary hereditary immunodeficiency condition caused by a defect in the nicotinamide adenine dinucleotide phosphate (NADP) oxidase complex. Recurrent infections and inflammatory complications with a narrow bacterial and fungal spectrum characterize CGD. Acute inflammatory and infectious complications are vexing and fatal for them. Therefore, managing CGD with prophylactic antibiotics and antifungal agents is essential. Case Presentation: We present a 23-month-old infant with a chief complaint of recent lymphadenopathy diagnosed with CGD. Two months later, she was hospitalized with uncontrolled fever and lung involvement while receiving prophylactic treatment with trimethoprim/sulfamethoxazole. A mass-like consolidation was seen in her radiography evaluation. Based on the biopsy and bronchoalveolar lavage (BAL) pathology report, pulmonary mucormycosis was confirmed. Two weeks after starting the standard treatment regimen with amphotericin B, the patient’s symptoms improved. She was discharged in good general condition with oral voriconazole and trimethoprim/sulfamethoxazole and referred to do hematopoietic stem cell transplantation (HSCT). Conclusions: Mucormycosis in CGD is not a common infection and usually infects patients with impaired cell-mediated immunity, hematological malignancies, steroid treatment, and diabetes. Patients with CGD are vulnerable when treated with a high dose of immunosuppressant medications. In our case report, the patient was infected with mucormycosis despite not receiving immunosuppressant medications and having no history of hematologic malignancies or diabetes. Our patient also had a mass-like consolidation in her radiological result, a rare feature of pulmonary mucormycosis involvement in CGD patients.

Bronchioloalveolar Carcinoma Mimicking Section as Pneumonia: A Case Report

Bronchioloalveolar Carcinoma (BAC) also known as alveolar cell carcinoma is a subtype of adenocarcinoma that is more common in women and non smokers. It accounts for almost 5% of all lung cancers. Bronchioloalveolar carcinoma may appear as a wide variety ranging from solitary nodule to patchy, lobar or multilobar opacities. The mucinous, non mucinous, ambiguous or mixed are the histological types of BAC. The mucinous variety of BAC sometimes may present as a consolidation which is indistinguishable from an infective pneumonia on a radiological picture. Hereby, authors present a case of 65-year-old male patient, who was evaluated for non resolving pneumonia for a time span of one year. He presented to the Respiratory Medicine Outpatient Department with a cough and expectoration for the past nine months. Antibiotic courses did not provide the patient any sort of relief and there was no change in the size of the lesion. Chest X-ray has shown right sided non homogenous opacity and later Contrast Enhanced Computerised Tomography (CECT) thorax and biopsy (computed tomography-guided) was done from the same site for further evaluation. Cytology done from CT-guided biopsy sample showed typical lepidic growth pattern. Histopathologically, it showed mucinous variety of BAC. Usually, the patients have no symptoms but an abnormal chest X-ray, while a few have features like coughing with expectoration and pain in the chest. Only cytology or biopsy can help with a proper diagnosis, which can be done via needle biopsy (CT or fluoroscopy guided) or transbronchial biopsy and Bronchoalveolar Lavage (BAL). It has rarely been documented in the literature that BAC masquerades as a consolidation with very little change.

Secondary Infections among COVID-19 Hospitalised Patients and their Antimicrobial Susceptibility Pattern: A Cross-sectional Study in a Tertiary Care Hospital

Introduction: The novel coronavirus (2019-nCoV) is a contagious virus that causes respiratory infection and has shown evidence of human-to-human transmission. In this infection the immunity of the patient is decreased; making them susceptible to various secondary infections. This leads to increased morbidity and mortality in these patients. Aim: To estimate the profile of secondary infections in hospitalised Coronavirus Disease-2019 (COVID-19) patients and analyse their antimicrobial susceptibility pattern. Materials and Methods: A cross-sectional study was conducted for a period of five months from June to October 2021, which included COVID-19 positive patients with secondary infection admitted in the dedicated COVID hospital, Maharaja Krishna Chandra Gajapati Medical College and Hospital (MKCG MCH), Berhampur, Odisha, India. Clinical samples like blood, urine, sputum, tissue biopsy and Bronchoalveolar Lavage (BAL) were collected aseptically from patients with COVID-19 and were processed in microbiology laboratory as per standard operating procedures. All the necessary information like demographic features (age, gender), associated co-morbidities and oxygen saturation levels of COVID-19 positive patients at the time of admission were collected and entered in a Microsoft Excel sheet for further analysis. Results of continuous variables were described by mean and range while categorical variables were described by frequency. All the generated data was analysed by Statistical Package for the Social Sciences (SPSS) 16.0. Results: A total of 438 patients suspected of COVID-19 were admitted during the study period, out of which 138 patients were positive for COVID-19 by Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). Out of 138 COVID-19 positive patients, 105 patients were willing to give samples and their samples were processed for bacterial and fungal culture and sensitivity. Total 18/105 (17.1%) samples were positive for bacterial and fungal growth. Blood Stream Infection (BSI) were seen in 14/18 (77.8%) and was predominantly associated with Staphylococcus aureus 5/14 (35.7%), followed by Enterococcus spp. 3/14 (21.4%). Out of total culture positive cases, 2/18 (11.1%) showed Urinary Tract Infection (UTI). Of the UTI cases Escherichia coli was isolated from 1/2 (50%) of cases. Out of total culture positive cases, 2/18 (11.1%) were identified having mucormycosis. All gram positive bacteria had shown maximum resistant to ampicillin and gram negative bacteria were resistant to ampicillin-sulbactam, levofloxacin, cotrimoxazole. Conclusion: In COVID-19 positive patients with secondary infection, early diagnosis and prompt treatment will lead to improved patient care and better outcome.

Identification of a Novel HIF-1α-αMβ2 Integrin-NET Axis in Fibrotic Interstitial Lung Disease.

Neutrophilic inflammation correlates with mortality in fibrotic interstitial lung disease (ILD) particularly in the most severe form, idiopathic pulmonary fibrosis (IPF), although the underlying mechanisms remain unclear. Neutrophil function is modulated by numerous factors, including integrin activation, inflammatory cytokines and hypoxia. Hypoxia has an important role in inflammation and may also contribute to pulmonary disease. We aimed to determine how neutrophil activation occurs in ILD and the relative importance of hypoxia. Using lung biopsies and bronchoalveolar lavage (BAL) fluid from ILD patients we investigated the extent of hypoxia and neutrophil activation in ILD lungs. Then we used ex vivo neutrophils isolated from healthy volunteers and BAL from patients with ILD and non-ILD controls to further investigate aberrant neutrophil activation in hypoxia and ILD. We demonstrate for the first time using intracellular staining, HIF-1α stabilization in neutrophils and endothelial cells in ILD lung biopsies. Hypoxia enhanced both spontaneous (+1.31-fold, p < 0.05) and phorbol 12-myristate 13-acetate (PMA)-induced (+1.65-fold, p < 0.001) neutrophil extracellular trap (NET) release, neutrophil adhesion (+8.8-fold, <0.05), and trans-endothelial migration (+1.9-fold, p < 0.05). Hypoxia also increased neutrophil expression of the αM (+3.1-fold, p < 0.001) and αX (+1.6-fold, p < 0.01) integrin subunits. Interestingly, NET formation was induced by αMβ2 integrin activation and prevented by cation chelation. Finally, we observed NET-like structures in IPF lung sections and in the BAL from ILD patients, and quantification showed increased cell-free DNA content (+5.5-fold, p < 0.01) and MPO-citrullinated histone H3 complexes (+21.9-fold, p < 0.01) in BAL from ILD patients compared to non-ILD controls. In conclusion, HIF-1α upregulation may augment neutrophil recruitment and activation within the lung interstitium through activation of β2 integrins. Our results identify a novel HIF-1α- αMβ2 integrin axis in NET formation for future exploration in therapeutic approaches to fibrotic ILD.

Association of Submucosal Eosinophilia With Blood and Bronchoalveolar Lavage Eosinophilia in Adults With Severe Refractory Asthma

Abstract Objectives Asthma is a chronic inflammatory disease of the lungs, and for individuals with persistently uncontrolled symptoms despite maximal medical therapy, an endobronchial biopsy and bronchoalveolar lavage (BAL) may be obtained to guide therapy. Given the invasive nature of this procedure, most patients obtain blood eosinophil counts. The goal of this study was to compare blood, BAL, and biopsy eosinophils to identify whether there is a correlation between these various approaches. Methods A retrospective study was conducted in adult patients (n = 220) who had been seen in the Refractory Obstructive Lung Disease clinic over a 10-year period (2008-2017). All the patients had been clinically diagnosed with severe refractory asthma. Clinical data were obtained through review of the electronic medical records. Results Patients with submucosal eosinophilia had a greater prevalence of intraepithelial eosinophils (50.9% vs 2.3%, P &lt; .001), intraepithelial neutrophils (36.7% vs 9.3%, P &lt; .001), and intraepithelial lymphocytes (52.5% vs 18.6%, P &lt; .001). In contrast, no significant differences were noted between the samples with submucosal eosinophilia present versus submucosal eosinophilia absent for polymorphonuclear leukocyte (PMN) percent, lymphocyte percent, or macrophage percent in BAL. There was a significant difference in eosinophil percentage between the two groups (8.7% vs 1.1%, P = .004). When submucosal eosinophilia was divided into mild (1-10 eosinophils/HPF), moderate (11-20 eosinophils/HPF), and severe (&gt;20 eosinophils/HPF), mean eosinophilia trended more with eosinophilia in the BAL than with the peripheral blood. There was poor correlation (r = 0.31, P = .0001) between eosinophil levels in the blood and BAL. Conclusion Compared to BAL, histopathologic data may more accurately characterize the underlying pathophysiology in severe asthmatics by providing a more detailed quantification of the airway inflammatory infiltrates. Moreover, blood eosinophilia may not be as representative of airway inflammation in patients with severe refractory asthma given the poor correlation between eosinophil levels in the blood and BAL.

ACUTE BLASTOMYCOSIS PNEUMONIA CAUSING ARDS REQUIRING OPEN LUNG BIOPSY FOR IDENTIFICATION

SESSION TITLE: Chest Infections 2 SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/09/2018 01:15 PM - 02:15 PM INTRODUCTION: Blastomycosis is a systemic pyogranulomatous fungal infection usually affecting the lungs. Presenting symptoms are similar to other forms of acute pneumonia making disease identification difficult. CASE PRESENTATION: A 49-year-old male was hospitalized after 3 weeks of worsening dyspnea, fever, and non-productive cough despite two courses of antibiotics for suspected pneumonia. Within days, he decompensated requiring mechanical ventilation. His past medical history was negative for tobacco use and he denied immunocompromising illnesses. On physical exam, he was afebrile and normotensive. There was no jugular venous distention or peripheral edema. Auscultation revealed decreased breath sounds and diffuse crackles bilaterally. On mechanical ventilation, the patient had an oxygen saturation of 90% and PaO2 78 mmHg on FiO2 0.8 and PEEP 14. Workup revealed WBC 14 (x10ˆ3/uL) and normal procalcitonin. Bacterial, fungal and acid fast bacilli cultures of the blood were negative as well as respiratory viral panel and HIV. His chest X-ray showed diffuse bilateral alveolar and interstitial opacities and CT chest displayed bilateral ground-glass infiltrates. ANCA, ANA, and anti-GBM tests were negative. Echocardiogram and brain natriuretic peptide were normal. Bronchoscopy with transbronchial biopsy and bronchoalveolar lavage (BAL) was performed. BAL cytology had alveolar macrophages without malignant cells and a normal eosinophil count. BAL fluid had negative fungal, viral and bacterial cultures, along with negative fungal antigen and serology testing. Given that the transbronchial biopsy was unrevealing, an open lung biopsy was performed. The sample showed organizing diffuse alveolar damage, alveolar macrophages and broad-based budding yeast, all of which are consistent with Blastomyces infection. Amphotericin and high-dose corticosteroids were started with subsequent rapid improvement. He was discharged home with itraconazole and prednisone. DISCUSSION: Blastomycosis is endemic to the Mississippi and Ohio River basins, and Midwest states [1]. Infection depends on soil exposure in endemic areas; outbreaks with waterways and major highway projects [2]. Definitive diagnosis requires positive cultures. Sputum and BAL cultures result in diagnosis in 86% and 92% of patients, respectively; [1,2] while antigen testing yields 93% sensitivity and 79% specificity [3]. Blastomycosis pneumonia rarely causes acute respiratory distress syndrome (ARDS); however, when it does mortality rates are estimated at over 50%. Steroids may have benefit in fulminant cases, but study results have been mixed. Given the efficacy of culture and antigen testing, this is a rare case that required an open lung biopsy for diagnosis. CONCLUSIONS: This case of biopsy-proven acute blastomycosis organizing pneumonia with negative serum and BAL serology, antigen and culture resulting in ARDS demonstrates the risks of delayed identification. Reference #1: Azar, M. M., Assi, R., Relich, R. F., Schmitt, B. H., Norris, S., Wheat, L. J., & Hage, C. A. (2015). Blastomycosis in Indiana: Clinical and Epidemiologic Patterns of Disease Gleaned from a Multicenter Retrospective Study. Chest, 148(5), 1276–1284. https://doi.org/10.1378/chest.15-0289 Reference #2: Carlos, W. G., Rose, A. S., Wheat, L. J., Norris, S., Sarosi, G. A., Knox, K. S., & Hage, C. A. (2010). Blastomycosis in indiana: digging up more cases. Chest, 138(6), 1377–1382. https://doi.org/10.1378/chest.10-0627 Reference #3: Durkin, M., Witt, J., Lemonte, A., Wheat, B., & Connolly, P. (2004). Antigen assay with the potential to aid in diagnosis of blastomycosis. Journal of Clinical Microbiology, 42(10), 4873–4875. https://doi.org/10.1128/JCM.42.10.4873-4875.2004 DISCLOSURES: No relevant relationships by William Carlos, source=Web Response no disclosure on file for Rajat Kapoor; No relevant relationships by Jonathan Prest, source=Web Response

Predictive value of eosinophils and neutrophils on clinical effects of ICS in COPD.

Inflammation is present to a variable degree and composition in patients with COPD. This study investigates associations between both eosinophils and neutrophils in blood, sputum, airway wall biopsies and bronchoalveolar lavage (BAL) and their potential use as biomarkers for clinical response to inhaled corticosteroids (ICS). In total, 114 steroid-naïve COPD patients of the Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease (GLUCOLD) study using ICS or placebo during 30-month follow-up were included. Cell counts in blood, sputum, biopsies and BAL were evaluated at baseline. In addition, at baseline, 6 and 30 months, forced expiratory flow in 1 s (FEV1 ), residual volume/total lung capacity (hyperinflation) and Clinical COPD Questionnaire were evaluated. Cross-sectional analyses at baseline showed that higher blood eosinophils were significantly associated with higher eosinophil counts in sputum, biopsies and BAL. However, blood neutrophils did not significantly correlate with neutrophil counts in the other compartments. Baseline eosinophils and neutrophils, in whichever compartment measured, did not predict longitudinal FEV1 changes. Higher baseline biopsy eosinophils were associated with an increase in symptoms during 6- and 30-month ICS treatment. In addition, higher biopsy neutrophils were associated with a more marked reduction in hyperinflation during 6-month ICS treatment compared with placebo. Our findings indicate that blood eosinophils reflect eosinophils in other compartments, in contrast to neutrophils, in ICS-naïve COPD patients. Both baseline eosinophils and neutrophils do not predict ICS-induced lung function changes over a period of 6-30 months. The associations of biopsy eosinophils with worsening respiratory symptoms and biopsy neutrophils with improvement in hyperinflation during ICS treatment deserve further investigation.

Sulfur mustard triggers oxidative stress through glutathione depletion and altered expression of glutathione-related enzymes in human airways

Context: Sulfur mustard (SM) is a lipophilic and reactive chemical compound that targets human airway system.Objective: Glutathione (GSH) depletion, oxidative stress (OS) status, and changes in expression of GSH-dependent antioxidant enzymes were considered in human mustard lungs.Materials and methods: Lung biopsies and bronchoalveolar lavage (BAL) were collected from non-exposed (n = 10) individuals and SM-exposed patients (n = 12). Alterations in expression of GSH-dependent enzymes were studied using RT2 Profiler™ PCR array. OS was evaluated by determining BAL fluid levels of total antioxidant capacity (TAC), malondialdehyde (MDA), and GSH.Results: Mean TAC (0.142 ± 0.027 µmol/l) and GSH (4.98 ± 1.02 nmol/l) in BAL fluids of control group was significantly higher (p < .05) than those in SM-exposed patients (TAC = 0.095 ± 0.018 µmol/l and GSH= 3.09 ± 1.02 nmol/l), while MDA level in BAL fluids of these patients (0.71 ± 0.06 nmol/l) was significantly (p = .001) higher than that in controls (0.49 ± 0.048 nmol/l). Glutathione peroxidases (GPXs), glutathione-s-transferases (GSTs), and glutathione synthetase (GSS) enzymes were overexpressed in mustard lung biopsies, while glutathione reductase (GSR) was significantly downregulated (14.95-fold).Conclusions: GSH depletion induced by GSR downregulation may be a major mechanism of SM toxicity on human lung. Despite overexpression of GSTs and GPXs genes, GSH depletion may decline the productivity of these enzymes and total antioxidants capacity, which is associated with OS.

Nonspecific Interstitial Pneumonia: What Is the Optimal Approach to Management?

We reviewed current aspects of the clinical and pathogenic profile of nonspecific interstitial pneumonia (NSIP), to better elucidate the complex issue of management and treatment options for NSIP patients. Recent findings suggest that idiopathic NSIP is a complex clinical entity with a disease spectrum that includes at least three different phenotypes: NSIP associated with autoimmune features, emphysema, and familial interstitial lung disease. This distinction, based mainly on clinical findings, may be of critical importance when it comes to making a decision on patients' management. This hypothesis warrants further studies. Currently, two major radiologic-pathologic different profiles have been well established. First, the "inflammatory type" characterized by prominent lymphocytic inflammation both on biopsy and bronchoalveolar lavage (BAL), and high-resolution computed tomography (HRCT) with mixed NSIP/organizing pneumonia pattern that tends to have a better response to corticosteroid and immunosuppressive treatment. Second, the "highly fibrotic" subgroup that shows prominent reticular changes and traction bronchiectasis by HRCT, high fibrotic background on biopsy, and no lymphocytosis on BAL. The latter fibrotic NSIP is the subgroup with less potential to respond to immunosuppressive treatment and a marginal risk to evolve into "full-blown idiopathic pulmonary fibrosis." The management of patients with fibrotic, progressive, and immunosuppressive treatment, refractory NSIP remains uncertain, and further studies are needed to address the role of antifibrotic drug in this settings. Oxygen therapy, pulmonary rehabilitation, and lung transplantation are of importance in the current management of severe, progressive, and refractory NSIP patients.

Induced sputum deposition improves diagnostic yields of pulmonary alveolar proteinosis: A clinicopathological and methodological study of 17 cases

ABSTRACTPulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease characterized by the accumulation of intra-alveolar lipoprotein-like surfactants. Lung core biopsy and bronchoalveolar lavage (BAL) fluid are currently the two major sources of sampling for diagnosis. In the present study, we assessed the value of induced sputum in diagnosing PAP by transmission electron microscopy and examined the PAP 2-year death rate in Asians. Transmission electron microscopy was performed on the samples from 17 patients with PAP, 13 patients with inflammatory lung diseases, and 13 healthy adults. The PAP patients were followed up for 3–156 months, and inflammatory lung diseases patients or healthy adults for 12–36 months. The ultrastructural features including diagnostic lamellar bodies of induced sputum deposition (ISD) samples were similar to that of the BAL fluid sediment. However, the rates of lamellar bodies were 73.7% in the ISD group, significantly higher than the spontaneous sputum deposition (SSD) group (42.1%, P < .0487) and similar to the BAL sediment (76.2%) and the lung biopsy (54.5%) groups. The overall 2-year death rate of our PAP patients was 17.6% (3/17), not statistically different from the healthy adults and patients with inflammatory diseases (0/13, P = .237 for both). ISD may be the preferred non-invasive sampling method for diagnosing PAP by electronic microscopy because of the higher diagnostic yield than SSD. The diagnostic yields of this noninvasive method were similar to that of lung core biopsy and BAL.

Signs of immune activation and local inflammation are present in the bronchial tissue of patients with untreated early rheumatoid arthritis

ObjectivesEvents in the lungs might contribute to generation of anticitrullinated protein antibodies (ACPA) in rheumatoid arthritis (RA). We investigated if signs of immune activation are present in bronchial biopsies and...

Microlithiasis of Seminal Vesicles and Severe Oligoasthenospermia in Pulmonary Alveolar Microlithiasis (PAM): Report of An Unusual Sporadic Case.

Pulmonary alveolar microlithiasis (PAM) is classified as an elective dysmetabolic thesaurotic pneumoalveolitis and characterized by the presence within the alveoli of the lungs of myriad of tiny calculi. The classic presentation of the chest radiography is unmistakable with multiple small "sand-like" opacities diffusely involving both lung fields. We present a case of male infertility for hypoposia and severe oligoasthenospermia in a young patient with recurrent haematuria and small calcifications in the seminal vesicles similar to pulmonary microliths. PAM was diagnosed on routine chest radiography, com- puter tomography (CT), transbronchial biopsy and bronchoalveolar lavage (BAL).

Pulmonary infection with caseating mediastinal lymphadenitis caused by Mycobacterium gordonae

It is often difficult to discern true mycobacterial infection from colonization due to Mycobacterium gordonae (M. gordonae) since this organism is ubiquitous and is commonly an innocuous saprophyte. This study reports a rare case of caseating hilar adenopathy and pulmonary disease caused by M. gordonae in a patient with chronic obstructive pulmonary disease (COPD) and rheumatoid arthritis (RA) on maintenance steroids and methotrexate. Pathologic exam and cultures of lymph node excision biopsy and bronchoalveolar lavage (BAL) confirmed the diagnosis.Triple antimycobacterial therapy with azithromycin, ethambutol and rifabutin was administered. The patient had significant clinical and radiologic improvement and follow-up cultures confirmed microbiologic cure.Mycobacterium gordonae can be a rare cause of significant pulmonary infection, and positive sputum or BAL cultures for M. gordonae should not be automatically discarded and considered as nonpathogenic contaminants or colonizing organisms, especially in immunocompromised hosts with comorbidities. A detailed review of the case and relevant literature is provided.

Disconnect between sputum neutrophils and other measures of airway inflammation in asthma

To the Editor: Asthma heterogeneity has been described by the nature and intensity of granulocytic infiltration into the airways [1, 2]. Sputum, endobronchial biopsies and bronchoalveolar lavage (BAL) sample different anatomical regions of the airways. Few studies have directly compared the inflammatory cell infiltrates in these regions within a large cohort of moderate–severe asthma patients using standard techniques. In the BOBCAT (Bronchoscopic exploratory research study Of Biomarkers in Corticosteroid-refractory AsThma) study, we sampled multiple airway compartments concurrently, enabling us to evaluate relationships between granulocytic infiltrates within and between compartments in a large cohort of moderate–severe adult asthma patients. This prospective multicentre observational study was conducted in four visits over a 4–6 week period, as described previously [3]. The patients included had moderate–severe persistent asthma (forced expiratory volume in 1 s (FEV1) 40–80% predicted and Asthma Control Questionnaire (ACQ) [4] score >1.5) and, within the past 5 years, evidence of >12% post-bronchodilator reversibility or a provocative concentration of methacholine causing a 20% decline in FEV1 ≤8 mg·mL−1 despite high-dose inhaled corticosteroid (ICS) (≥1000 μg·day−1 fluticasone propionate equivalent) with or without long-acting β2-adrenergic agonist therapy. Key exclusion criteria included initiation or increase in systemic steroid use 30 days prior to screening, chronic or recent (within the past 30 days) use of immunosuppressive therapies, or other active lung disease. Patients had a prior established diagnosis of moderate–severe asthma for ≥6 months prior to screening while receiving a stable dose regimen (>6 weeks) of a high-dose ICS. Allowed concomitant medications included leukotriene receptor antagonists and oral corticosteroids. 78 patients with confirmed moderate–severe asthma were enrolled at 18 sites; 67 (86%) completed the study. All patients had persistently impaired …

S100A7/psoriasin expression in the human lung: unchanged in patients with COPD, but upregulated upon positive S. aureusdetection

BackgroundProgressive airway inflammation and susceptibility to the airway colonisation and infection are characteristic for the pathophysiology of chronic obstructive pulmonary disease (COPD). Antimicrobial peptides (AMPs) are central to the function of the innate host immune response against microbial pathogens and are regulators of inflammation and immunity. S100A7/psoriasin, a recently described AMP, is an essential component of the human epithelia against invading pathogens and acts as an effector molecule of the host innate defence in the skin. We hypothesized that S100A7/psoriasin is involved in the airway mucosal immunity and differently regulated and expressed in the lung during progression of COPD.MethodsS100A7/psoriasin gene expression was assessed in bronchial biopsies and bronchoalveolar lavage (BAL) fluid cells of healthy controls and COPD patients. Using confocal microscopy and immunohistochemistry, the protein expression of S100A7/psoriasin was investigated.ResultsHere, we report that S100A7/psoriasin, the major antimicrobial peptide of the human skin, is constitutively expressed in perinuclear granules of human bronchial epithelial cells and alveolar macrophages. Whereas typical activators of the innate immune response like TLR ligands and cytokines induced the upregulation of CXCL-8 mRNA and release of CXCL-8 by epithelial cells, S100A7/psoriasin mRNA expression was not modulated. To investigate a potential association of S100A7/psoriasin with COPD, S100A7/psoriasin mRNA expression was assessed in bronchial biopsies and BAL fluid cells of patients at different stages of COPD and controls. Overall, 10 healthy individuals and 34 COPD patients were enrolled in this study. We found an association of S100A7/psoriasin mRNA expression with bacterial detection in the tracheobronchial system (p = 0.0304), which was the strongest in individuals positive for with S. aureus (p = 0.0005). However, S100A7/psoriasin mRNA expression was not altered during the progression of COPD.ConclusionsS100A7/psoriasin gene expression is unchanged in the airways during COPD. The newly identified association of S100A7/psoriasin with S. aureus may provide new insights into the antimicrobial defence response of the human airways, leading to the induction of S100A7/psoriasin upon microbial challenge.

Increased pulmonary Wnt (wingless/integrated)-signaling in patients with sarcoidosis

Sarcoidosis is an inflammatory multisystemic granulomatous disease of unknown aetiology commonly affecting the lungs, and pulmonary fibrosis often develops in chronic sarcoidosis. It has been suggested that Wnt (Wingless/integrated)-signaling has a role in inflammatory and fibrotic processes in the lungs, but its role in sarcoidosis has not been investigated. We hypothesised that Wnts secreted from T cells or other inflammatory cells have a role in the pathogenesis of sarcoidosis. Brush biopsies and bronchoalveolar lavage (BAL) were obtained through bronchoscopy from healthy controls (n = 18) and patients with sarcoidosis (n = 48). Semi-quantitative RT-PCR, electrophoretic mobility shift assay (EMSA) and immunocytochemistry were performed to analyse Wnt expression and activation of the Wnt-signal transducer β-catenin. Altered expression of Wnt5A, Wnt7A and Wnt7B mRNA in BAL cells was observed, as well as an increased activation of β-catenin, measured by EMSA and confirmed with immunocytochemistry, in resident lung cells from patients with sarcoidosis. More pronounced changes in Wnt expression were seen with advancing disease stage. Thus, by three independent methods, we have found evidence of increased pulmonary Wnt-activation in sarcoidosis. In the lungs of patients with sarcoidosis there is a previously unappreciated increased Wnt-signal activation that could contribute to the inflammatory processes.

Montelukast added to fluticasone propionate does not alter inflammation or outcomes

Airway inflammation is a key pathological feature of asthma which underlies its clinical presentation. To examine whether adding a leukotriene modifier to an inhaled corticosteroid produces further clinical and/or anti-inflammatory benefits in patients symptomatic on short-acting beta(2)-agonists. Patients uncontrolled on short-acting beta(2)-agonists were treated for 12 weeks with either fluticasone propionate (100mcg BD) or fluticasone propionate (100mcg BD) and montelukast (10mg QD) in a randomized, double-blind, parallel group study. Bronchoscopy with endobronchial biopsy and bronchoalveolar lavage (BAL) was performed before and after treatment to compare effects on airway inflammation. Of 103 subjects enrolled, 89 subjects completed treatment and 82 subjects had matched pair biopsy samples. Submucosal eosinophil counts, the primary endpoint, and asthma control improved to similar extents after both treatments (p<or=0.008). Both treatments significantly reduced submucosal mast cell, CD3+, CD4+, CD8+ and CD25+ cell counts. Submucosal mast cell reduction was greater in the fluticasone propionate plus montelukast group. There were no differences between treatments in BAL markers of inflammation or thickness of sub-epithelial collagen. Low-dose fluticasone propionate significantly improves clinical disease control and reduces airway inflammation in asthma patients uncontrolled with short-acting beta(2)-agonists without further improvement when montelukast is added to low-dose fluticasone propionate.

Increased vascular permeability precedes cellular inflammation as asthma control deteriorates

Airway microcirculation is abnormal in asthma but the role of vascular changes in asthma deteriorations remains poorly defined. We prospectively assessed the vascular changes accompanying worsening of asthma control by using an inhaled corticosteroid (ICS) dose-reduction model. To evaluate airway vascularity, vascular permeability and expression of vascular endothelial growth factor (VEGF) in early asthma deterioration induced by ICS back-titration. Twenty mild-to-moderate persistent symptomatic asthmatics on low-to-moderate ICS were recruited and treated with 4 weeks of high-dose fluticasone propionate (1000 microg/day) to achieve symptom control. This was followed by dose reduction to half of the pre-study doses for 4-8 weeks until the symptoms began to return. Endobronchial biopsy and bronchoalveolar lavage (BAL) samples were obtained after both treatment periods. Vascularity as measured by the number and size of blood vessels, as well as VEGF expression did not change following ICS reduction. Even on high-dose ICS, perivascular albumin staining and BAL microalbumin levels in asthmatic subjects, as markers of permeability, were elevated when compared with normal subjects and both further increased significantly after ICS reduction. There was a significant association between changes in vascular leakiness and clinical deterioration. Increases in airway albumin correlated with previously reported increases in airway wall infiltration with T lymphocytes. Our results suggest that airway vascular leakage is a major pathophysiologic feature of early asthma deterioration, occurring before recrudescence of cellular inflammation.