Smokers with asthma have epithelial changes that are associated with increased asthma symptoms, such as shortness of breath and phlegm production. The fact that epithelial characteristics in ex-smokers are similar to those in never-smokers suggests that the smoke-induced changes can be reversed by smoking cessation.

In view of the associations of "a disintegrin and metalloprotease" (ADAM) with respiratory diseases, we assessed the expression of various ADAMs in human lung tissue. Lung tissue was obtained from nine individuals who underwent surgery for lung cancer or underwent lung transplantation for emphysema. Also, 16HBE 14o-(human bronchial epithelial) and A549 (alveolar type II epitheliumlike) cell lines were used. Immunohistochemistry was performed with antibodies recognizing different ADAM domains. The ADAMs were typically distributed over the bronchial epithelium. ADAM8 and ADAM10 were expressed diffusely in all layers of the epithelium. ADAM9, ADAM17, and ADAM19 were predominantly expressed in the apical part of the epithelium, and ADAM33 was predominantly and strongly expressed in basal epithelial cells. In smooth muscle, ADAM19 and ADAM17 were strongly expressed, as was ADAM33, though this expression was weaker. ADAM33 was strongly expressed in vascular endothelium. All ADAMs were generally expressed in inflammatory cells. The typical distribution of ADAMs in the lung, especially in the epithelium, is interesting and suggests a localized function. As most ADAMs are involved in release of (pro-) inflammatory mediators and growth factors, they may play an important role in the first line of defense and in initiation of repair events in the airways.

The splenic marginal zone of adult humans contains B cells, of which most express CD27, an antigen only recently identified as a marker for somatically mutated memory B cells. We investigated whether and to which extent the developing marginal zone in infants and children is populated by either memory (CD27+) or naive (CD27-) B cells. Frozen sections of 32 spleens of infants and children ranging in age from 6 days to 15 years and 6 adult spleens were investigated. The expression of CD27 in combination with monoclonal antibodies against CD3, CD21, IgM, IgD and ASM-1 was analyzed by immunohistochemistry. The marginal zone was already present at 4 months after birth but CD21 expression was observed first after 2 years. CD27-positive marginal zone B cells were observed firstly 2 years after birth and increased in number to adult levels at the age of 5 years. We demonstrated that the MZ of infants and young children is populated by naive B cells, which are replaced by memory B cells in a time frame of 2 to 5 years. Before the age of 2 years, although present, memory B cells appear to be unable to colonize the marginal zone. Because of the absence of memory B cells in the marginal zone, the immune system of a child is not capable to initiate a rapid secondary humoral immune response comparable to the adult immune response.

CoR is still accompanied by airway abnormalities because BM thickness is similar in individuals with asthma with CoR, ClinR, and CuA without ICS. Airway eosinophilic activation best differentiates these three groups, signifying their importance in the clinical expression and severity of bronchial hyperresponsiveness in asthma.