Inhaled Steroids, Circulating Eosinophils, Chronic Airway Infection, and Pneumonia Risk in Chronic Obstructive Pulmonary Disease. A Network Analysis.

Rationale: Treatment of chronic obstructive pulmonary disease (COPD) with inhaled corticosteroids (ICS) is controversial, because it can reduce the risk of future exacerbations of the disease at the expense of increasing the risk of pneumonia.Objectives: To assess the relationship between the presence of chronic bronchial infection (CBI), reduced number of circulating eosinophils, ICS treatment, and the risk of pneumonia in patients with COPD.Methods: This was a post hoc long-term observational study of an historical cohort of 201 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease II-IV) who were carefully characterized (including airway microbiology) and followed for a median of 84 months. Results were analyzed by multivariate Cox regression and network analysis.Measurements and Main Results: Mean age was 70.3 years, 90.5% of patients were male, mean FEV1 was 49%, 71.6% of patients were treated with ICS, 57.2% of them had bronchiectasis, and 20.9% had <100 blood eosinophils/µl. Pathogenic microorganisms were isolated in 42.3% of patients, and 22.4% of patients fulfilled the definition of CBI. During follow-up, 38.8% of patients suffered one or more episodes of pneumonia, with CBI (hazard ratio [HR], 1.635) and <100 eosinophils/µl (HR, 1.975) being independently associated with the risk of pneumonia, particularly when both coexist (HR, 3.126). ICS treatment increased the risk of pneumonia in those patients with <100 eosinophils/µl and CBI (HR, 2.925).Conclusions: Less than 100 circulating eosinophils/µl combined with the presence of CBI increase the risk of pneumonia in patients with COPD treated with ICS.

Lost in the Clinics and Found in the Morgue: A Case of Peripheral T-cell Lymphoma Masquerading as Pneumonia.

In modern medicine, there is an increasing dependence on noninvasive imaging modalities, for diagnosis and management of diseases. Though there are definite advantages to this, they are at times offset by diagnostic pitfalls especially in entities with elusive clinical presentation.Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) is an aggressive subtype of T-cell lymphomas that does not meet criteria for a specific subtype. Peripheral T-cell lymphoma usually has varied clinical presentations depending on the site of involvement. Vast majority of PTCL patients present with systemic disease, generalized lymphadenopathy and constitutional symptoms. Pulmonary involvement is relatively rare and is seen in approximately 10% of patients.Here in we highlight a rare case of PTCL, masquerading as pneumonia due to extensive pulmonary involvement that went undiagnosed and was discovered at autopsy. This case of malignant lymphoma of T-cell origin involving the lung, which is very rare, highlights the continued importance of medical autopsies not only as a teaching tool but also as an important adjunct to investigative medicine in uncovering lapses that can subsequently be avoided to improve patient care and decrease mortality.

Dysregulation of claudin-5 in HIV-induced interstitial pneumonitis and lung vascular injury. Protective role of peroxisome proliferator-activated receptor-γ.

RATIONALE: HIV-1-induced interstitial pneumonitis (IP) is a serious complication of HIV-1 infection, characterized by inflammation and cellular infiltration in lungs, often leading to respiratory failure and death. The barrier function of the pulmonary endothelium is caused in part by tight junction (TJ) proteins, such as claudin-5. Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in lung tissues and regulates inflammation. We hypothesize that HIV-1 induces vascular lung injury, and HIV-1-mediated damage of the pulmonary endothelium and IP is associated with dysregulation of PPAR-γ. OBJECTIVES: Investigate the effects of HIV-1 infection on the pulmonary microvasculature and the modulatory effects of the PPAR-γ ligands. METHODS: Using human lung tissues, we demonstrated down-regulation of claudin-5 (marker of pulmonary barrier integrity), down-regulation of PPAR-γ transcription, and expression in lung tissues of HIV-1-infected humans with IP. MEASUREMENTS AND MAIN RESULTS: Human lung microvascular endothelial cells expressed the TJ proteins claudin-5, ZO-1, and ZO-2; HIV-1 decreased TJ proteins expression and induced nuclear factor-κB promoter activity, which was reversed by PPAR-γ agonist. Using two murine HIV/AIDS models, we demonstrated decreased claudin-5 expression and increased macrophage infiltration in the lungs of HIV-1-infected animals. Activation of PPAR-γ prevented HIV-1-induced claudin-5 down-regulation and significantly reduced viremia and pulmonary macrophage infiltration. CONCLUSIONS: HIV-induced IP is associated with injury to the lung vascular endothelium, with decreased TJ and PPAR-γ expression, and increased pulmonary macrophage infiltration. PPAR-γ ligands abrogated these effects. Thus, regulation of PPAR-γ can be a therapeutic approach against HIV-1-induced vascular damage and IP in infected humans. Removal of Expression of Concern: Issues leading to the previous expression of concern for this article have been resolved after further revisions and editorial review. No further concerns exist.

Atypical severe combined immunodeficiency caused by a novel homozygous mutation in Rag1 gene in a girl who presented with pyoderma gangrenosum: a case report and literature review.

Severe combined immunodeficiency (SCID) is a heterogeneous group of inherited defects involving the development of T- and/or B-lymphocytes. We report a female with atypical severe combined immunodeficiency caused by a novel homozygous mutation at cDNA position 2290 (c.2290C > T) in exon 2 of the RAG1 gene. The patient presented with bronchopneumonia, pyoderma gangrenosum (PG), pancytopenia and splenomegaly. She presented to us with pancytopenia and splenomegaly at the age of 11. Her condition was complicated by PG on left lower ankle at the age of 12. She experienced bronchopneumonia at the age of 15. She was diagnosed with RAG1 deficiency at the age of 16. Her immunological presentation included leucopenia and diminished number of B cells.

Clinical features and phylogenetic analysis of Coxsackievirus A9 in Northern Taiwan in 2011.

BACKGROUND: Coxsackievirus A9 (CA9) was one of the most prevalent serotype of enteroviral infections in Taiwan in 2011. After several patient series were reported in the 1960s and 1970s, few studies have focused on the clinical manifestations of CA9 infections. Our study explores and deepens the current understanding of CA9. METHODS: We analyzed the clinical presentations of 100 culture-proven CA9-infected patients in 2011 by reviewing their medical records and depicted the CA9 phylogenetic tree. RESULTS: Of the 100 patients with culture-proven CA9 infections, the mean (SD) age was 4.6 (3.4) years and the male to female ratio was 1.9. For clinical manifestations, 96 patients (96%) had fever and the mean (SD) duration of fever was 5.9 (3.4) days. Sixty one patients (61%) developed a skin rash, and the predominant pattern was a generalized non-itchy maculopapular rash without vesicular changes. While most patients showed injected throat, oral ulcers were found in only 19 cases (19%), among whom, 6 were diagnosed as herpangina. Complicated cases included: aseptic meningitis (n=8), bronchopneumonia (n=6), acute cerebellitis (n=1), and polio-like syndrome (n=1). Phylogenetic analysis for current CA9 strains is closest to the CA9 isolate 27-YN-2008 from the border area of mainland China and Myanmar. CONCLUSIONS: The most common feature of CA9 during the 2011 epidemic in Taiwan is generalized febrile exanthema rather than herpangina or hand, foot, and mouth disease. Given that prolonged fever and some complications are possible, caution should be advised in assessing patients as well as in predicting the clinical course.

Computed tomography findings of influenza A (H1N1) pneumonia in adults: pattern analysis and prognostic comparisons.

AIM: The aim of this study was to evaluate retrospectively the chest computed tomography findings of influenza A (H1N1) pneumonia and their relationship with clinical outcome. METHODS: Chest computed tomography findings and clinical outcomes of 76 patients with influenza A (H1N1) pneumonia were assessed. Computed tomography findings were evaluated for the presence and distribution of parenchymal abnormalities, which were then classified into 3 patterns: bronchopneumonia, cryptogenic organizing pneumonia (COP), and acute interstitial pneumonia (AIP) patterns. Clinical courses were divided into 2 groups on the basis of necessitating admission to intensive care unit or mechanical ventilation therapy (group 1) or not (group 2). RESULTS: Lung abnormalities consisted of ground-glass opacity (93%, 71 patients), consolidation (66%, 50 patients), small nodules (61%, 46 patients), and tree-in-bud sign (22%, 17 patients). Lesions were classified into bronchopneumonia (49%, 37 patients), COP (30%, 23 patients), AIP (18%, 14 patients), and unclassifiable (3%, 2 patients) patterns. Patients with AIP pattern had a tendency to belonging to group 1, accounting for 40% (8 of 20 patients) of group 1 course and only 11% (6 of 56 patients) of group 2 course (P = 0.004). CONCLUSIONS: Computed tomography findings of influenza A (H1N1) pneumonia in adults can be classified into COP, AIP, and bronchopneumonia patterns. Patients presenting with AIP pattern have a tendency to show poor prognosis.

[Extra medullary hematopoiesis associated to congenital dyserythropoietic anemia II in adult]. / Hématopoïèse extramédullaire associée à une dysérythropoïèse congénitale II chez l'adulte.

The congenital dyserythropoietic anemias comprise a group of rare hereditary disorders of erythropoiesis characterized by anemia with ineffective erythropoiesis and morphological abnormalities of erythroblasts in the bone marrow. Congenital dyserythropoietic anemia type II or HEMPAS is the more frequent type. It is rare in adults. Extra medullary hematopoiesis is also a rare entity; it is a physiological response to chronic anemia observed in certain hemopathies like congenital dyserythropoietic anemia type II. We report the observation of a patient for who diagnosis of extra medullary hematopoiesis associated to congenital dyserythropoietic type II was made in adulthood.

Pulmonary langerhans cell histiocytosis masquerading as tuberculosis in an infant.

A 4-month-old infant presented with continued fever, unresolving bronchopneumonia and household contact with sputum-smear-positive tuberculosis (TB) and showed marginal improvement on anti-TB chemotherapy. Recurrent pneumothorax prompted the clinical diagnosis of TB to be revised. High-resolution CT scan of the chest and open lung biopsy confirmed the diagnosis of pulmonary Langerhans cell histiocytosis. Treatment with prednisolone and vinblastin resulted in settling of fever and resolution of respiratory symptoms and signs. In communities where the prevalence of TB is high, unusual presentations should prompt consideration of alternative diagnoses.

Death of a 6-month-old due to a tracheal bronchus.

The death of an infant younger than 1 year requires a thorough scene investigation and autopsy. Most infant deaths investigated by forensic pathologists can be placed into 2 general categories: sudden infant death syndrome and accidental asphyxial deaths. Despite the fact that most infant deaths occur within these 2 categories, it is important to remember that other entities may be responsible for death. In this report, we present a developmental pulmonary abnormality that was ultimately responsible for the death of an infant. A 6-month-old male infant with a prior history of pneumonia was brought to an emergency department for evaluation of fever. Antibiotics were prescribed, and the child was discharged and sent home with instructions to his mother to follow up with his pediatrician. Later that evening, the infant seemed to be in respiratory distress. His mother again transported him to the emergency department, where, on arrival, he became apneic. Despite vigorous resuscitative efforts, the infant died. Of note at autopsy was the presence of low-set abnormal ears and bilateral inward-turning ankles. Internally, an abnormality of the tracheobronchial tree was evident, with the right upper lobe bronchus arising from the distal trachea, proximal to the carina. In addition, the right upper lobe was discolored and firm. Microscopically, pneumonia was present. The cause of death was pneumonia due to a right tracheal bronchus. Childhood pneumonia is a known cause of childhood hospitalization, morbidity, and mortality. Identifying the causes of recurrent pneumonia, be it structural, metabolic, or syndromic, aids in preventing recurrent infections and reducing the incidence of childhood mortality. A tracheal bronchus, also known as bronchus suis or "pig bronchus," is an anatomic variant of the tracheobronchial tree in which a bronchus arises proximal to the carina, most commonly on the right and predominantly in males. The incidence is around 0.2%. Although the tracheal bronchus is sometimes a clinically silent entity, some patients may exhibit certain signs and symptoms, including hemoptysis, coughing, stridor, wheezing, and pain. The typical consequences of the tracheal bronchus are recurrent pneumonias. The recurrent pneumonia is thought to be due to a stasis of secretions and an abnormal pulmonary clearing mechanism. Treatment for the condition varies, based on symptoms. For asymptomatic patients, conservative management is adequate. For symptomatic patients with persistent atelectasis or right upper lobe consolidation, surgical excision is advised.

Pneumomediastinum and subcutaneous emphysema in a cat associated with necrotizing bronchopneumonia caused by feline herpesvirus-1.

This report describes a 1-year-old cat with acute dyspnea. Thoracic radiography revealed a pneumomediastinum and severe subcutaneous emphysema. Lower airway surgical exploration was unable to determine the cause. At postmortem examination, acute necrotizing bronchopneumonia and fibrinonecrotic tracheitis due to feline herpesvirus-1 were diagnosed.

Phenotypic characterization of chronic inflammation in a rare case of endobronchial carcinoma.

This report presents a phenotypical characterization of the immune cell infiltrate in a rare case of endobronchial carcinoma. A patient initially treated for an adenocarcinoma of the esophagus developed an endobronchial carcinoma surrounded by gastric metaplasia distal to a suspected gastrobronchial fistula, 11 years after esophagectomy. Our hypothesis is that the sustained exposure of the bronchial mucosa to a mixed acid and pancreatobiliary refluxate led to chronic inflammation and promoted malignant transformation. We performed an immunohistochemical study of the tumor microenvironment evaluating the density of CD3(+), CD8(+) T lymphocytes, CD20(+) B lymphocytes, CD68(+) macrophages and FoxP3(+) regulatory T cells. Quantification of immune cell density was completed using a novel software-based analysis method. Our results suggest that, within all the tissues analyzed, FoxP3(+) regulatory T cells were present at their highest density in the malignant and metaplastic tissues. The endobronchial metaplasia biopsied several years prior to the detection of the endobronchial adenocarcinoma was already densely infiltrated by B cells and macrophages, when compared to the immune cell infiltrate of the endobronchial carcinoma. Altogether, these observations support the current understanding of carcinogenesis promoted by chronic inflammation.

Severe histiolymphocytic and heterophilic bronchopneumonia as a reaction to in ovo fowlpox vaccination in broiler chicks.

Broiler chickens on several farms from a single poultry company experienced neurological signs and mortality in chicks between 3 days and 10 days of age over a 3-week period after use of a fowlpox-vectored infectious laryngotracheitis virus vaccine in ovo. At necropsy the lungs contained numerous tan or gray, opaque to translucent, 0.5- to 2.0-mm nodules in the parenchyma. Microscopic lesions were a multifocal severe lymphohistiocytic and heterophilic bronchopneumonia. Immunohistochemistry was positive for fowlpox virus in macrophages and lymphocytes, and polymerase chain reaction on paraffin-embedded lung tissues was positive for a fowlpox vector virus commonly used as a vaccine. The cause of the neurological signs was not determined.

Fatal anorectal trauma in the setting of sexual assault: case report and literature survey.

Homicides exclusively due to genital trauma have not been widely reported, and anorectal trauma in sexual assaults is uncommon. We describe a case of a 45-year-old white woman who sustained devastating homicidal colorectal trauma that served as a primary cause of death in the setting of rape. Our patient sustained a 15-cm laceration of the anterior rectal wall and ultimately died of peritonitis and sepsis. Death from rectal perforation and sepsis in the setting of sexual assault is rare and has only been documented in 3 other cases, 2 pediatric patients and 1 elderly debilitated patient. Other representative and unique methods of perforation are reviewed along with a brief discussion of the development of peritonitis after perforating colorectal trauma.

[Radiographic and computed tomographic manifestations of chest in patients with acute chlorine gas poisoning].

OBJECTIVE: To investigate the radiographic and computerized tomographic features of chest in patients with acute chlorine poisoning and its diagnostic value. METHODS: Twenty-eight cases of chlorine poisoning were reviewed. And their radiographic and computerized tomographic features were compared and analyzed. RESULTS: Radiographic findings: among 28 patients, 9 cases were normal and 2 cases had no abnormalities on the first chest X-ray and became abnormal one or two days later. And there were abnormal findings in first chest X-ray in 17 patients:acute tracheal inflammation of peribronchitis (n = 3), acute chemical bronchopneumonia (n = 6) and diffuse interstitial and central pulmonary edema (n = 8). CT manifestations: At Days 1-3, the patients of mild poisoning had scattered patchy dense shadow; those of moderate to severe poisoning showed multiple patchy or diffuse infiltration (ground-glass opacity). And partial consolidation, air bronchogram and pleural effusion could be observed. At Days 4-10, the manifestations of mild poisoning were largely absorbed; those of moderate to severe poisoning manifested the absorption of diffuse or multiple patchy effusion and a fading of shadow. And the size of lung consolidation became smaller than before. At Day 10 after onset, 4 patients completely recovered. At Days 30-40, 6 cases showed traces of fibrous shadow and one case showed small punctiform opacities in both lungs. And at Day 42, there was slight ground-glass change. CONCLUSION: Acute chlorine gas poisoning in varying degrees may manifest acute bronchial pneumonia and acute pulmonary edema. During treatment, a series of chest X-ray examinations will help to follow the changes of disease. And CT examination can offer a more accurate evaluation of lung lesions.

A practice-based survey of mortality revisited - what trends in end-of-life care are emerging?

The gathering of mortality data in general practice is useful and important; it provides a vital insight into local health needs, highlights gaps in service provision and educates those working in general practice. This article considers the mortality rates in Chorley Wood Health Centre between 2008 and 2009. The survey results provide an interesting insight into local trends, one key factor being the rate of people being enabled to die at home.

[Autopsy case of corticosteroid-induced invasive pulmonary aspergillosis with cavity-formation].

Invasive pulmonary aspergillosis (IPA) is an important and fatal complication in the patients with neutropenic or immunosuppressed condition. In spite of intensive treatment with anti-fungal drugs, the prognosis of the patients who have been suffered from IPA is extremely poor. This case was an 85-year-old Japanese man who was diagnosed as idiopathic thrombocytopenic purpura (ITP). He underwent high-dose corticosteroids and gamma-globulin therapy. During the hospitalization, he complained respiratory symptoms, and the abnormal shadow suggesting pulmonary infiltration and cavitation was pointed out on chest imaging. He was diagnosed as IPA because of high level of serum beta-D-glucan and positive for aspergillus antigen. Although he underwent intensive care with anti-fungal drug administration and artificial respiration, he died of respiratory distress on the 68th hospitalization. Postmortem examination disclosed severe bronchopneumonia, cavitation and pulmonary arterial thrombi in both lungs. Histological examination showed widely distributed epitheloid cell granulomata with central necrosis containing aspergillus hyphae, and vasodestructive growth of fungus with occasional organized thrombi.

[Cannabis and the lung - chill or kill?]. / Cannabis und Lunge - Chill or Kill?

Cannabis is the most widely consumed illicit drug in the western world. Cannabis and tobacco smoke contain a similar mix of irritant and toxic chemicals. Therefore, there are reasons to suspect, that cannabis and tobacco have similar side effects. However, the pulmonary effects of smoking cannabis have not been extensively researched and the few findings are contradictory. Among the reasons for this uncertainty are its illegal status and the common practice of combining cannabis with tobacco. Separating the effects of the two substances is therefore difficult.

[Pathological anatomy in A/H1N1 influenza].

Forty autopsy cases died from A/H1N1 influenza in Moscow, the Moscow Region, and Chita were analyzed. Major changes were found to develop in the trachea and lung. The lung showed the pattern of exudative and proliferative stages of diffuse alveolar lesion. In addition, the signs of viremia-associated infectious-toxic shock, as suggested by pronounced changes in the brain, kidneys, liver, spleen, adrenals, and lymph nodes were revealed. Bacterial bronchopneumonia was detected only in 20% of cases.

Lysosomal stability during phagocytosis of Aspergillus flavus spores by alveolar macrophages of cortisone-treated mice.

Control mice and those treated with cortisone were exposed to aerosols of viable spores of Aspergillus flavus. Fifteen to 20 minutes later, animals were killed, and alveolar macrophages were obtained by tracheobronchial lavage. Electron-microscopic examination of these cells revealed that, whereas the lysosomes of control macrophages showed extensive attraction and fusion with the phagocytic membranes surrounding spores, the lysosomes of macrophages from animals treated with cortisone revealed little, if any, interaction. This diminished lysosomal response in forming phagocytic vacuoles may be important in the subsequent development of hyphal bronchopneumonia which frequently, occurs in cortisonetreated mice exposed to spores of A. flavus.