John Faul

Bio: John Faul is an academic researcher from Connolly Hospital Blanchardstown. The author has contributed to research in topics: Vitamin D and neurology & Asthma. The author has an hindex of 22, co-authored 41 publications receiving 2163 citations. Previous affiliations of John Faul include Memorial Hospital of South Bend.

Interleukin-17–producing innate lymphoid cells and the NLRP3 inflammasome facilitate obesity-associated airway hyperreactivity

Abstract: The mechanisms underlying the association between obesity and the development of asthma remain incompletely understood. Dale T. Umetsu and his colleagues report that the number of IL-17A+ type 3 innate lymphoid cells (ILCs) is increased in the lungs of mice fed a high-fat diet. Activation of the NLRP3 inflammasome in lung macrophages promotes IL-1β production and ILC development, and blockade of IL-1 signaling inhibits airway hyperreactivity in obese mice. As these ILCs are also found in the lungs of individuals with asthma, these results suggest that this pathway may be targeted in asthma.

CD4+ invariant T-cell-receptor+ natural killer T cells in bronchial asthma.

Abstract: Background Bronchial asthma is associated with an inflammatory process that is characterized by the presence in the airways of large numbers of CD4+ T cells producing interleukin-4 and interleukin-13. However, the CD4 antigen is expressed not only by class II major histocompatibility complex (MHC)–restricted CD4+ T cells, but also by a newly identified subgroup of T cells, CD1d-restricted natural killer T cells. These cells express a conserved (invariant) T-cell receptor and have a potent immunoregulatory function. Because mouse models of allergic asthma indicate that natural killer T cells are required for the development of allergen-induced airway hyperreactivity, we hypothesized that natural killer T cells play an important role in human asthma. Methods We used CD1d-tetramers, antibodies specific for natural killer T cells, as well as reverse-transcriptase–polymerase-chain-reaction analysis of the invariant T-cell receptor of natural killer T cells to assess the frequency and distribution of natural killer T cells in the lungs and in the circulating blood of 14 patients with asthma. Results About 60 percent of the pulmonary CD4+CD3+ cells in patients with moderate-tosevere persistent asthma were not class II MHC–restricted CD4+ T cells but, rather, natural killer T cells. The natural killer T cells expressed an invariant T-cell receptor and produced type 2 helper cytokines. In contrast, the CD4+ T cells found in the lungs of patients with sarcoidosis were conventional CD4+CD3+ T cells, not natural killer T cells. Conclusions Together with studies in mice indicating a requirement for natural killer T cells in the development of allergen-induced airway hyperreactivity, our results strongly suggest that CD4+ natural killer T cells play a prominent pathogenic role in human asthma.

Activated, Cytotoxic CD8+ T Lymphocytes Contribute to the Pathology of Asthma Death

Abstract: This study investigates the presence of CD8+ T lymphocytes and their possible association with viral infection in bronchi of victims of fatal asthma. Postmortem samples from the peribronchial region of the lung were obtained from seven patients who died an asthma death (AD), seven asthmatic patients who died of unrelated causes (AUC), and seven postmortem cases with no history of lung disease (control subjects). Using immunohistochemical techniques, the CD8+ cytotoxic T-cell population in peribronchial tissue was characterized in three patient groups. The percentage of CD8+ cells expressing the activation marker CD25 was higher in the AD group than in both the AUC and control groups (11.91 ± 1.92% versus 3.93 ± 1.63% and 1.09 ± 0.56%, respectively (p < 0.001). Perforin expression, a marker of cytotoxicity, was highest in the AD group (9.16 ± 1.5%) compared with 1.39 ± 0.9; 1.8 ± 0.6% in the AUC and control groups respectively (p < 0.001). Expression of interleukin-4 (IL-4) and interferon gamma (IFN- γ ) b...

Update on Diagnosis and Management

Abstract: Ticks are capable of transmitting viruses, bacteria, protozoa, and rickettsiae to man. Several of these tick-borne pathogens can lead to pulmonary disease. Characteristic clinical features, such as erythema migrans in Lyme disease, or spotted rash in a spotted fever group disease, may serve as important diagnostic clues. Successful management of tick-borne diseases depends on a high index of suspicion and recognition of their clinical features. Patients at risk for tick bites may be coinfected with two or more tick-borne pathogens. A Lyme vaccine has recently become available for use in the United States. Disease prevention depends on the avoidance of tick bites. When patients present with respiratory symptoms and a history of a recent tick bite or a characteristic skin rash, a differential diagnosis of a tick-borne pulmonary disease should be considered. Early diagnosis and appropriate antibiotic therapy for these disorders lead to greatly improved outcomes. (CHEST 1999; 116:222‐230)

Lung immunopathology in cases of sudden asthma death

Abstract: The histopathology of airway inflammation in rare cases of sudden asphyxic asthma death (SAAD) is unclear. This study examines, for the first time, the relative disposition of lymphocyte and macrophage subsets and eosinophils in proximal and distal tissues of such cases. Multiple resection specimens from five cases of SAAD were studied. Tissue blocks were obtained at necroscopy and immediately frozen in liquid nitrogen within 18 hours of death (death occurring within 1 h of the onset of an unprovoked asphyxic asthma attack). After immunohistological staining, frozen sections underwent semi-quantitative analysis (cell counts per unit area) for T-cells, macrophages and eosinophils using computerized imaging systems. Subsets of T-cells and macrophages were estimated using double immunofluorescence techniques. Variability within samples, between samples and between cases was compared. These cases of fatal asthma showed infiltrates of T-cells, macrophages and eosinophils within peribronchial tissues. Distinct from stable asthma, a CD8+ T-cell dominance was found. A high proportion of eosinophils were activated (EG2+), whereas the relative proportion of antigen-presenting cells (RFD1+) did not seem to be abnormal, although numbers of these cells were high. These features were seen both in proximal and distal tissues. The variability of these parameters within an individual was 9.4-15.2%, however, the variability between individual cases was greater. Sudden asphyxic asthma is associated with inflammatory infiltrates both of proximal and distal lung tissues. In contrast to stable asthma, this infiltrate contains large numbers of CD8+ T-cells, suggesting distinct qualitative as well as quantitative characteristics in the immunopathology of sudden asthma death.

Atherosclerosis — An Inflammatory Disease

Abstract: Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall; however, it is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations,2,3 cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.4,5 In fact, the lesions of atherosclerosis represent . . .

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Abstract: Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.