Eosinophilia and symptomatic pulmonary amyloidosis.

The case of a man with progressive breathlessness and pulmonary infiltration caused by AL amyloidosis associated with multiple myeloma is presented. There was a marked peripheral eosinophilia, which has not previously been described with amyloidosis.

Subepithelial immunopathology of the large airways in smokers with and without chronic obstructive pulmonary disease.

Previous work has shown an increase in CD8+ T-cells, neutrophils and eosinophils in small airway subepithelium in smokers. The authors have now investigated whether similar changes occur in the large airways. Immunohistochemistry on frozen sections of bronchial biopsies were obtained at bronchoscopy in 11 nonsmokers, eight asymptomatic smokers and 11 smokers with chronic bronchitis and chronic obstructive pulmonary disease (COPD). There was an increase in the number of CD8+ cells infiltrating the bronchial subepithelium in the COPD group compared to the asymptomatic smokers (305 (109-400) versus 92 (41-550) cells x mm(-2), p=0.030). There was a negative correlation between the number of CD8+ cells and the forced expiratory volume in one second (FEV1) %predicted (p=0.005, r=-0.62), and a positive correlation between the number of CD8+ cells and the number of pack years smoked (p=0.017, r=0.42). There was a negative correlation between the activated/total eosinophils ratio and the FEV1 % pred (p=0.017, r=-0.51). There was a negative correlation between pack years smoked and the number of neutrophils (p=0.022, r=-0.36). Smokers who develop chronic obstructive pulmonary disease have increased numbers of CD8+ T-cells in large airways when compared to asymptomatic smokers. Airway obstruction was associated with an increase in the proportion of eosinophils that were activated.

Immunopathology of the small-airway submucosa in smokers with and without chronic obstructive pulmonary disease.

The airflow obstruction in chronic obstructive pulmonary disease (COPD) occurs mainly at the level of the small airways. In order to investigate the effect of smoking on small-airway submucosal immunopathology, we used immunohistochemistry in peripheral lung sections obtained at surgery from a group of smokers (n = 22) and from a group of nonsmokers (n = 22) that contained both ex-smokers (n = 17) and lifelong nonsmokers (n = 5). Subjects were also divided into those with (n = 19) and those without (n = 20) airflow obstruction. We found an increase in total eosinophils (p = 0.001) and activated eosinophils (p = 0.010), an increase in the CD8(+)/CD3(+) cell ratio (p = 0.003), and a decrease in the CD4(+)/CD8(+) cell ratio (p = 0.005) among cells infiltrating the small-airway submucosa in an area 50 micrometers deep to the basement membrane in smokers as compared with nonsmokers. There was also an increase in neutrophils (p = 0.019) when smokers were compared with lifelong nonsmokers. Neutrophil numbers correlated with numbers of eosinophils (p = 0.0003, r = 0.58). Furthermore, the CD8(+)/CD3(+) cell ratio was related to pack-years smoked (p = 0.016, r = 0.36), months since smoking cessation (p = 0.003, r = 0.47), and number of infiltrating eosinophils (p = 0.007, r = 0.43) and neutrophils (p = 0.004, r = 0.44). These findings suggest that smoking induces movement of an inflammatory infiltrate into the submucosa of the small airway, the location of the increased resistance to airflow in COPD.

Expression of interleukin-5 and granulocyte-macrophage colony-stimulating factor in aspirin-sensitive and non-aspirin-sensitive asthmatic airways.

Increased numbers of eosinophils and mast cells in the bronchial mucosa are characteristic features in subjects with aspirin-sensitive asthma. Interleukin-5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are involved in the activation, maturation, and perpetuation of survival of eosinophils. Immunohistochemical techniques were therefore used to study the expression of IL-5 and GM-CSF on frozen bronchial biopsies from 13 aspirin-sensitive asthmatic (ASA) and 8 non-ASA (NASA) subjects. Aspirin sensitivity was diagnosed by lysine-aspirin inhalation provocation. ASA airways demonstrated a significant 2-fold increase in the total number of submucosal inflammatory cells expressing IL-5 (p = 0.03) and approximate 4- and 2-fold increases in the numbers of mast cells expressing IL-5 and GM-CSF (p = 0.02 and p = 0.04, respectively). There was also a 4-fold increase in the number of eosinophils expressing IL-5 (p = 0.004). These results suggest a central role for the mast cell and eosinophil in regulation of the inflammatory cell infiltrate of ASA airways by secretion of the hemopoietic cytokines IL-5 and GM-CSF.

Loss of transmitter-associated enzyme staining following axotomy does not indicate death of brainstem cholinergic neurons.

To assess the validity of using loss of transmitter-associated enzyme staining to document the death of injured cholinergic neurons, vagal and hypoglossal cholinergic neurons were quantitatively identified at 7 and 28 days following unilateral axotomy using staining procedures for choline acetyltransferase (ChAT) or acetylcholinesterase (AChE), using Nissl stains, and using the retrogradely transported dye, True blue, as an intracellular marker. At 7 days post-axotomy, the transmitter-associated enzymes, ChAT and AChE, had disappeared from over 95% of vagal neurons (P greater than 0.001) and from over 50% of hypoglossal neurons (P greater than 0.001) as compared with the unlesioned control side. At 28 days post-axotomy, ChAT and AChE were still absent from over 70% of vagal neurons (P greater than 0.001) but only from about 15% of hypoglossal neurons as compared with unlesioned control sides. In contrast, no statistically significant losses of either vagal or hypoglossal neurons were found at 7 or 28 days post-axotomy using Nissl stains or detection of retrogradely transported True blue. These findings indicate that transmitter-associated enzyme expression can be regulated independently of neuronal survival following injury. We conclude that absence of transmitter-associated enzyme staining is not an absolute indicator of death of cholinergic neurons.