Diogenes S. Ferreira

Toll-like receptors 2, 3 and 4 and thymic stromal lymphopoietin expression in fatal asthma

Airway inflammation in asthma involves innate immune responses. Toll‐like receptors (TLRs) and thymic stromal lymphopoietin (TSLP) are thought to be involved in airway inflammation, but their expression in asthmatics’ both large and small airways has not been investigated.

Extracellular matrix in airway smooth muscle is associated with dynamics of airway function in asthma

Altered deposition of extracellular matrix (ECM) in the airway smooth muscle (ASM) layer as observed in asthma may influence ASM mechanical properties. We hypothesized that ECM in ASM is associated with airway function in asthma. First, we investigated the difference in ECM expression in ASM between asthma and controls. Second, we examined whether ECM expression is associated with bronchoconstriction and bronchodilation in vivo.

Pulmonary periarterial inflammation in fatal asthma.

Background To date, little information has been available about pulmonary artery pathology in asthma. The pulmonary artery supplies the distal parts of the lungs and likely represents a site of immunological reaction in allergic inflammation. The objective of this study was to describe the inflammatory cell phenotype of pulmonary artery adventitial inflammation in lung tissue from patients who died of asthma.

Characterization of autopsy-proven fatal asthma patients in São Paulo, Brazil

Few data are available on autopsy-proven fatal asthma patients in São Paulo, Brazil. We characterized 73 asthma patients who were autopsied at the Serviço de Verificação de Obitos da Universidade de São Paulo between 1996 and 2004. An interview with the next of kin assessed socioeconomic status, history, and treatment of asthma. There were 42 women and 31 men. Fifty-six (76.7%) of them were older than 34 years. Sixty-three percent were Caucasians, 77.3% had < 8 years of schooling, and the median income was 1.6 times the minimum wage. Twenty-two patients (30.1%) were smokers and 14 (19.2%) were ex-smokers. Only 25 (34.2%) patients were regularly followed by a doctor. Only 12.3% received inhaled steroids. Thirty-five patients (47.9%) had moderate-to-severe asthma. Fifty-five (75.3%) deaths took place outside a hospital. We conclude that this population shares characteristics of severe or poorly controlled asthma, low educational and socioeconomic levels, and lack of medical care and of inhaled steroid use.

Airway dimensions in fatal asthma and fatal COPD: overlap in older patients.

Abstract In some patients with chronic asthma clinical and physiological similarities with COPD may exist, such as partial reversibility to bronchodilators and persistent expiratory airflow obstruction. However, pathological data comparing both diseases in patients of similar age and disease severity are scarce. We compared large and small airway dimensions in 12 younger (mean age 32 yrs) and 15 older (mean age 65 yrs) non-smoker adult fatal asthma patients with 14 chronic smokers with severe, fatal COPD (mean age 71 yrs). Using H&E, Movat pentachrome staining and image analysis, we quantified large airway basement membrane (BM) thickness (μm), submucosal gland area and large and small airway inner wall, smooth muscle and outer wall areas. Areas were normalized by BM perimeter (μm2/μm). Younger adult fatal asthma patients had thicker BM, smooth muscle, and outer wall areas in both small and large airways when compared to COPD patients. In older asthmatics there was an overlap in BM thickness and airway structure in small airways. Inner wall layer in large and small airway level and submucosal gland areas were similar among groups. In conclusion, there are airway histological structural similarities between fatal asthma and fatal COPD. Older fatal asthmatics present overlapping airway structural features with younger adult fatal asthmatics and severe COPD patients. Our data contributes to a better understanding of asthma pathology in the elderly.

Bronchopulmonary lymph nodes and large airway cell trafficking in patients with fatal asthma

BACKGROUND Immune responses in asthmatic patients involve coordinated cellular responses in the airways and lymph nodes (LNs). However, no studies have described the composition of different cell populations in the bronchopulmonary LNs of asthmatic patients. OBJECTIVE We sought to investigate the expression of dendritic cells (DCs) and costimulatory molecules, B cells, T cells, TH2-related cytokines, eosinophils, and vascular cell adhesion molecule in the bronchopulmonary LNs and large airways of asthmatic patients. METHODS Using histochemistry, immunohistochemistry, and image analysis, we investigated the expression of Factor XIIIa(+), CD1a(+), CD83(+), and CD207(+) DCs; CD4(+) and CD8(+) T cells; CD20(+) B cells; CD23(+) (FcεRII) cells; IL-4; IL-5; eosinophils, and vascular cell adhesion molecule 1 in the large airways and bronchopulmonary LNs of 11 nonsmokers who died from an asthma exacerbation (fatal asthma [FA]) in comparison with 8 nonasthmatic control subjects. In selected cases of FA, we analyzed the coexpression of HLA-DR, CD40, and CD80 in lung and LN eosinophils. RESULTS The LNs of asthmatic patients exhibited increased density of eosinophils. No other cells were expressed differently in the LNs of patients with FA. The large airways of patients with FA had increased expression of eosinophils in all layers and increased expression of Factor XIIIa(+) cells, CD4(+) and CD8(+) T cells, CD20(+) B cells, and CD23(+) cells in the outer layer. There was colocalization of HLA-DR, CD40, and CD80 in the eosinophils at both sites. CONCLUSIONS FA is associated with the increased presence of eosinophils in the LNs and large airways, which express HLA-DR and costimulatory molecules. The expression of Factor XIIIa(+) monocyte-derived DCs, CD4(+) and CD8(+) T cells, CD20(+) B cells, and CD23(+) cells was increased in the large airways without a corresponding increase in the expression of these cells in the bronchopulmonary LNs. These findings support the concept that eosinophils might act as antigen-presenting cells in patients with FA.

Airway pathology in severe asthma is related to airflow obstruction but not symptom control

Patients with asthma present structural and inflammatory alterations that are believed to play a role in disease severity. However, airway remodeling and inflammation have not been extensively investigated in relation to both symptom control and airflow obstruction in severe asthmatics. We aimed to investigate several inflammatory and structural pathological features in bronchial biopsies of severe asthmatics that could be related to symptom control and airflow obstruction after standardized treatment.